Um estudo para testar a adição do medicamento cabozantinib à quimioterapia em pacientes com osteossarcoma recém-diagnosticado
Um estudo de viabilidade e randomizado de fase 2/3 do inibidor VEFGR2/MET Cabozantinib em combinação com quimioterapia citotóxica para osteossarcoma recém-diagnosticado
This phase II/III trial tests the safety, side effects, and best dose of the drug cabozantinib in combination with standard chemotherapy, and to compare the effect of adding cabozantinib to standard chemotherapy alone in treating patients with newly diagnosed osteosarcoma. Cabozantinib is in a class of medications called kinase inhibitors which block protein signals affecting new blood vessel formation and the ability to activate growth signaling pathways. This may help slow the growth of tumor cells. The drugs used in standard chemotherapy for this trial are methotrexate, doxorubicin, and cisplatin (MAP). Methotrexate stops cells from making DNA and may kill tumor cells. It is a type of antimetabolite. Doxorubicin is in a class of medications called anthracyclines. It works by slowing or stopping the growth of tumor cells in the body. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Adding cabozantinib to standard chemotherapy may work better in treating newly diagnosed osteosarcoma.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
PRIMARY OBJECTIVES:
I. To determine the feasibility of adding cabozantinib S-malate (cabozantinib) to standard MAP (high dose methotrexate, doxorubicin hydrochloride [doxorubicin], and cisplatin) chemotherapy in patients with newly diagnosed metastatic osteosarcoma with a resectable primary tumor.
II. To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survival (EFS) than MAP chemotherapy alone in patients with localized, resectable osteosarcoma.
III. To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survival (EFS) than MAP chemotherapy alone in patients with metastatic, pelvic and unresectable osteosarcoma.
SECONDARY OBJECTIVES:
I. To determine whether MAP chemotherapy plus cabozantinib results in more favorable overall survival (OS) than MAP chemotherapy alone in patients with localized, resectable osteosarcoma.
II. To determine whether MAP chemotherapy plus cabozantinib results in more favorable overall survival (OS) than MAP chemotherapy alone in patients with metastatic, pelvic and unresectable osteosarcoma.
III. To prospectively validate that elevated circulating tumor DNA (ctDNA) levels greater than or equal to 5% at the time of diagnosis are associated with increased risk of EFS-event in patients with localized, resectable osteosarcoma.
IV. To prospectively validate that elevated ctDNA levels greater than or equal to 5% at the time of diagnosis are associated with increased risk of EFS-event in patients with metastatic, pelvic and unresectable osteosarcoma.
V. To prospectively validate that elevated ctDNA levels greater than or equal to 3% after initiation of therapy and prior to definitive surgery are associated with increased risk of EFS-event in patients with localized, resectable osteosarcoma.
VI. To prospectively validate that elevated ctDNA levels greater than or equal to 3% after initiation of therapy and prior to definitive surgery are associated with increased risk of EFS-event in patients with metastatic, pelvic and unresectable osteosarcoma.
VII. To determine whether MAP chemotherapy plus cabozantinib results in increased symptom burden and decreased tolerability to patients as measured by patient reported therapy-specific acute toxicities (Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events [PRO-CTCAE]).
EXPLORATORY OBJECTIVES:
I. To determine the rate of good histologic response (> 90%) of resected primary tumor specimens following neoadjuvant chemotherapy with MAP plus cabozantinib and compare with response rates for MAP chemotherapy alone.
II. To describe the toxicities of the addition of cabozantinib to MAP chemotherapy in patients with newly diagnosed osteosarcoma.
III. To compare the probability of Grade 3 or higher port site wound complications on the MAP plus cabozantinib regimen to that of MAP chemotherapy alone in patients with newly diagnosed osteosarcoma who received a port for the administration of chemotherapy.
IV. To describe frequency of application of local control methods (surgery, hypofractionated stereotactic body radiotherapy, or radiofrequency ablation) for extrapulmonary metastatic osteosarcoma.
V. To compare total cumulative delivered doses of MAP chemotherapy agents between standard and experimental arms across multiple phases of therapy.
VI. To assess the pharmacokinetics of cabozantinib when administered concomitantly with standard chemotherapy agents during feasibility.
VII. To collect pulmonary metastatic lesions, paired primary tumor tissue, and serial blood samples for tumor profiling, liquid biopsies, and future testing of correlative biology studies.
VIII. To determine whether ctDNA at diagnosis and early on-treatment, as a continuous measurement of ctDNA burden, is associated with an increased risk of EFS-event in patients with newly diagnosed osteosarcoma.
IX. To evaluate whether the magnitude of change in ctDNA levels from diagnosis to planned surgical procedure is associated with risk of EFS-event in patients with newly diagnosed osteosarcoma.
X. To determine whether ctDNA levels greater than or equal to 3% after planned surgical procedures are associated with increased risk of EFS-event.
XI. To describe the presence of specific copy-number alterations, including MYC amplifications, detected in ctDNA and matched diagnostic tumor samples in patients with newly diagnosed osteosarcoma and determine whether frequently occurring copy-number alterations are associated with increased risk of EFS-event.
XII. To determine whether ctDNA burden is predictive of response to the experimental therapy in patients with newly diagnosed osteosarcoma.
XIII. To prospectively compare the impact of combination therapy on symptom bother as measured by the Functional Assessment of Cancer Therapy-General Questionnaire (FACT-G) item GP5 in patients with osteosarcoma receiving MAP chemotherapy with or without cabozantinib, and to assess the relationship between symptom bother and number of patient-reported acute toxicities (as measured by the PRO-CTCAE).
OUTLINE: This is a dose-escalation study of cabozantinib (Feasibility Phase) followed by a randomized phase II/III study (Efficacy Phase).
FEASIBILITY PHASE (CLOSED TO ACCRUAL 05/09/2025): Patients receive cabozantinib orally (PO), methotrexate intravenously (IV), doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles. Patients are then considered for appropriate local control. Then they receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle, followed by cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle, and cabozantinib PO, methotrexate IV, and doxorubicin IV for two 35-day cycles. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles.
EFFICACY PHASE: Patients with standard risk osteosarcoma are randomized to Arm A or Arm B. Patients with high risk osteosarcoma are randomized to Arm C or Arm D.
ARM A: Standard risk patients receive methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles.
ARM B: Standard risk patients receive cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive one 35-day "consolidation" cycle with methotrexate IV, doxorubicin IV, and cisplatin IV, then a second 35-day "consolidation" cycle with cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV, followed by two additional 35-day "consolidation" cycles with cabozantinib PO, methotrexate IV, and doxorubicin IV. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles.
ARM C: High risk patients receive methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles.
ARM D: High risk patients receive cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive one 35-day "consolidation" cycle with methotrexate IV, doxorubicin IV, and cisplatin IV, then a second 35-day "consolidation" cycle with cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV, followed by two additional 35-day "consolidation" cycles with cabozantinib PO, methotrexate IV, and doxorubicin IV. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles.
All patients also undergo X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
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Contactos e Locais
Locais de estudo
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New South Wales
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Randwick, New South Wales, Austrália, 2031
- Sydney Children's Hospital
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Westmead, New South Wales, Austrália, 2145
- The Children's Hospital at Westmead
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Queensland
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South Brisbane, Queensland, Austrália, 4101
- Queensland Children's Hospital
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South Australia
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North Adelaide, South Australia, Austrália, 5006
- Women's and Children's Hospital-Adelaide
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Victoria
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Clayton, Victoria, Austrália, 3168
- Monash Medical Center-Clayton Campus
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Parkville, Victoria, Austrália, 3052
- Royal Children's Hospital
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Western Australia
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Perth, Western Australia, Austrália, 6009
- Perth Children's Hospital
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Québec, Canadá, G1V 4G2
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
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Alberta
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Calgary, Alberta, Canadá, T3B 6A8
- Alberta Children's Hospital
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Edmonton, Alberta, Canadá, T6G 2B7
- University of Alberta Hospital
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Manitoba
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Winnipeg, Manitoba, Canadá, R3E 0V9
- CancerCare Manitoba
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Nova Scotia
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Halifax, Nova Scotia, Canadá, B3K 6R8
- IWK Health Centre
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Ontario
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London, Ontario, Canadá, N6A 5W9
- Children's Hospital
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Ottawa, Ontario, Canadá, K1H 8L1
- Children's Hospital of Eastern Ontario
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Toronto, Ontario, Canadá, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Canadá, H3H 1P3
- The Montreal Children's Hospital of the MUHC
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Montreal, Quebec, Canadá, H3T 1C5
- Centre Hospitalier Universitaire Sainte-Justine
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Sherbrooke, Quebec, Canadá, J1H 5N4
- Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
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Saskatchewan
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Saskatoon, Saskatchewan, Canadá, S7N 0W8
- Jim Pattison Children's Hospital
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Alabama
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Birmingham, Alabama, Estados Unidos, 35233
- Children's Hospital of Alabama
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Arizona
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Mesa, Arizona, Estados Unidos, 85202
- Banner Children's at Desert
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Phoenix, Arizona, Estados Unidos, 85054
- Mayo Clinic Hospital in Arizona
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Phoenix, Arizona, Estados Unidos, 85016
- Phoenix Childrens Hospital
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Tucson, Arizona, Estados Unidos, 85719
- Banner University Medical Center - Tucson
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Arkansas
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Little Rock, Arkansas, Estados Unidos, 72202-3591
- Arkansas Children's Hospital
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California
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Downey, California, Estados Unidos, 90242
- Kaiser Permanente Downey Medical Center
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Duarte, California, Estados Unidos, 91010
- City of Hope Comprehensive Cancer Center
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Loma Linda, California, Estados Unidos, 92354
- Loma Linda University Medical Center
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Long Beach, California, Estados Unidos, 90806
- Miller Children's and Women's Hospital Long Beach
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Los Angeles, California, Estados Unidos, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, Estados Unidos, 90027
- Children's Hospital Los Angeles
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Los Angeles, California, Estados Unidos, 90095
- Mattel Children's Hospital UCLA
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Madera, California, Estados Unidos, 93636
- Valley Children's Hospital
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Oakland, California, Estados Unidos, 94609
- UCSF Benioff Children's Hospital Oakland
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Oakland, California, Estados Unidos, 94611
- Kaiser Permanente-Oakland
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Orange, California, Estados Unidos, 92868
- Children's Hospital of Orange County
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Palo Alto, California, Estados Unidos, 94304
- Lucile Packard Children's Hospital Stanford University
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Sacramento, California, Estados Unidos, 95817
- University of California Davis Comprehensive Cancer Center
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San Diego, California, Estados Unidos, 92123
- Rady Children's Hospital - San Diego
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San Francisco, California, Estados Unidos, 94158
- UCSF Medical Center-Mission Bay
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Children's Hospital Colorado
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Denver, Colorado, Estados Unidos, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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Connecticut
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Hartford, Connecticut, Estados Unidos, 06106
- Connecticut Children's Medical Center
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New Haven, Connecticut, Estados Unidos, 06520
- Yale University
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Delaware
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Wilmington, Delaware, Estados Unidos, 19803
- Alfred I duPont Hospital for Children
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District of Columbia
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Washington D.C., District of Columbia, Estados Unidos, 20010
- Children's National Medical Center
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Washington D.C., District of Columbia, Estados Unidos, 20007
- MedStar Georgetown University Hospital
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Florida
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Fort Myers, Florida, Estados Unidos, 33908
- Golisano Children's Hospital of Southwest Florida
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Gainesville, Florida, Estados Unidos, 32610
- UF Health Cancer Institute - Gainesville
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Hollywood, Florida, Estados Unidos, 33021
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
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Jacksonville, Florida, Estados Unidos, 32207
- Nemours Children's Clinic-Jacksonville
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Miami, Florida, Estados Unidos, 33155
- Nicklaus Children's Hospital
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Miami, Florida, Estados Unidos, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Miami, Florida, Estados Unidos, 33176
- Miami Cancer Institute
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Orlando, Florida, Estados Unidos, 32827
- Nemours Children's Hospital
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Orlando, Florida, Estados Unidos, 32803
- AdventHealth Orlando
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Orlando, Florida, Estados Unidos, 32806
- Arnold Palmer Hospital for Children
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Pensacola, Florida, Estados Unidos, 32504
- Nemours Children's Clinic - Pensacola
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St. Petersburg, Florida, Estados Unidos, 33701
- Johns Hopkins All Children's Hospital
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Tampa, Florida, Estados Unidos, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
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Georgia
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Atlanta, Georgia, Estados Unidos, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
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Augusta, Georgia, Estados Unidos, 30912
- Augusta University Medical Center
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Savannah, Georgia, Estados Unidos, 31404
- Memorial Health University Medical Center
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Hawaii
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Honolulu, Hawaii, Estados Unidos, 96826
- Kapiolani Medical Center for Women and Children
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Idaho
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Boise, Idaho, Estados Unidos, 83712
- Saint Luke's Cancer Institute - Boise
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Northwestern University
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, Estados Unidos, 60612
- University of Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Lurie Children's Hospital-Chicago
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Peoria, Illinois, Estados Unidos, 61637
- OSF Children's Hospital of Illinois
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Springfield, Illinois, Estados Unidos, 62702
- Southern Illinois University School of Medicine
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202
- Riley Hospital for Children
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Iowa
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Des Moines, Iowa, Estados Unidos, 50309
- Blank Children's Hospital
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Iowa City, Iowa, Estados Unidos, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Kentucky
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Lexington, Kentucky, Estados Unidos, 40536
- University of Kentucky/Markey Cancer Center
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Louisville, Kentucky, Estados Unidos, 40202
- Norton Children's Hospital
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Louisiana
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New Orleans, Louisiana, Estados Unidos, 70121
- Ochsner Medical Center Jefferson
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New Orleans, Louisiana, Estados Unidos, 70118
- Children's Hospital New Orleans
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Maine
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Bangor, Maine, Estados Unidos, 04401
- Eastern Maine Medical Center
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Scarborough, Maine, Estados Unidos, 04074
- Maine Children's Cancer Program
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Maryland
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Baltimore, Maryland, Estados Unidos, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, Estados Unidos, 21215
- Sinai Hospital of Baltimore
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Baltimore, Maryland, Estados Unidos, 21201
- University of Maryland/Greenebaum Cancer Center
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Bethesda, Maryland, Estados Unidos, 20889-5600
- Walter Reed National Military Medical Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital Cancer Center
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Worcester, Massachusetts, Estados Unidos, 01655
- UMass Memorial Medical Center - University Campus
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- C S Mott Children's Hospital
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Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan Rogel Cancer Center
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Brownstown, Michigan, Estados Unidos, 48183
- Henry Ford Cancer Institute-Downriver
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Clinton Township, Michigan, Estados Unidos, 48038
- Henry Ford Macomb Hospital-Clinton Township
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Dearborn, Michigan, Estados Unidos, 48126
- Henry Ford Medical Center-Fairlane
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Detroit, Michigan, Estados Unidos, 48202
- Henry Ford Hospital
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Detroit, Michigan, Estados Unidos, 48201
- Children's Hospital of Michigan
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Grand Rapids, Michigan, Estados Unidos, 49503
- Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
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Jackson, Michigan, Estados Unidos, 49201
- Allegiance Health
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Kalamazoo, Michigan, Estados Unidos, 49007
- Bronson Methodist Hospital
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Novi, Michigan, Estados Unidos, 48377
- Henry Ford Medical Center-Columbus
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Royal Oak, Michigan, Estados Unidos, 48073
- Corewell Health Children's
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West Bloomfield, Michigan, Estados Unidos, 48322
- Henry Ford West Bloomfield Hospital
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Wyandotte, Michigan, Estados Unidos, 48192
- Henry Ford Wyandotte Hospital
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
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Minneapolis, Minnesota, Estados Unidos, 55455
- University of Minnesota/Masonic Cancer Center
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic in Rochester
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Mississippi
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Jackson, Mississippi, Estados Unidos, 39216
- University of Mississippi Medical Center
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Missouri
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Columbia, Missouri, Estados Unidos, 65212
- University of Missouri Children's Hospital
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Kansas City, Missouri, Estados Unidos, 64108
- Children's Mercy Hospitals and Clinics
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St Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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St Louis, Missouri, Estados Unidos, 63141
- Mercy Hospital Saint Louis
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St Louis, Missouri, Estados Unidos, 63104
- Cardinal Glennon Children's Medical Center
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68198
- University of Nebraska Medical Center
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Omaha, Nebraska, Estados Unidos, 68114
- Children's Hospital and Medical Center of Omaha
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Nevada
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Las Vegas, Nevada, Estados Unidos, 89144
- Summerlin Hospital Medical Center
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Las Vegas, Nevada, Estados Unidos, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
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New Hampshire
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Lebanon, New Hampshire, Estados Unidos, 03756
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
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New Jersey
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Hackensack, New Jersey, Estados Unidos, 07601
- Hackensack University Medical Center
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Morristown, New Jersey, Estados Unidos, 07960
- Morristown Medical Center
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New Brunswick, New Jersey, Estados Unidos, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
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Newark, New Jersey, Estados Unidos, 07112
- Newark Beth Israel Medical Center
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Paterson, New Jersey, Estados Unidos, 07503
- Saint Joseph's Regional Medical Center
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New York
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Albany, New York, Estados Unidos, 12208
- Albany Medical Center
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Buffalo, New York, Estados Unidos, 14263
- Roswell Park Cancer Institute
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Mineola, New York, Estados Unidos, 11501
- NYU Langone Hospital - Long Island
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New Hyde Park, New York, Estados Unidos, 11040
- The Steven and Alexandra Cohen Children's Medical Center of New York
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Estados Unidos, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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New York, New York, Estados Unidos, 10065
- NYP/Weill Cornell Medical Center
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New York, New York, Estados Unidos, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Rochester, New York, Estados Unidos, 14642
- University of Rochester
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Stony Brook, New York, Estados Unidos, 11794
- Stony Brook University Medical Center
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Syracuse, New York, Estados Unidos, 13210
- State University of New York Upstate Medical University
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The Bronx, New York, Estados Unidos, 10467
- Montefiore Medical Center - Moses Campus
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Valhalla, New York, Estados Unidos, 10595
- New York Medical College
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27599
- UNC Lineberger Comprehensive Cancer Center
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Charlotte, North Carolina, Estados Unidos, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Charlotte, North Carolina, Estados Unidos, 28204
- Novant Health Presbyterian Medical Center
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Charlotte, North Carolina, Estados Unidos, 28210
- Atrium Health Pineville/LCI-Pineville
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Durham, North Carolina, Estados Unidos, 27710
- Duke University Medical Center
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Greenville, North Carolina, Estados Unidos, 27834
- East Carolina University
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Winston-Salem, North Carolina, Estados Unidos, 27157
- Wake Forest University Health Sciences
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North Dakota
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Fargo, North Dakota, Estados Unidos, 58122
- Sanford Broadway Medical Center
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Ohio
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Akron, Ohio, Estados Unidos, 44308
- Children's Hospital Medical Center of Akron
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Cincinnati, Ohio, Estados Unidos, 45229
- Cincinnati Children's Hospital Medical Center
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Cleveland, Ohio, Estados Unidos, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, Estados Unidos, 44106
- Rainbow Babies and Childrens Hospital
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Columbus, Ohio, Estados Unidos, 43205
- Nationwide Children's Hospital
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Columbus, Ohio, Estados Unidos, 43210
- Ohio State University Comprehensive Cancer Center
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Dayton, Ohio, Estados Unidos, 45404
- Dayton Children's Hospital
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Toledo, Ohio, Estados Unidos, 43606
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, Estados Unidos, 97239
- Oregon Health and Science University
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Portland, Oregon, Estados Unidos, 97227
- Legacy Emanuel Children's Hospital
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Pennsylvania
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Danville, Pennsylvania, Estados Unidos, 17822
- Geisinger Medical Center
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Hershey, Pennsylvania, Estados Unidos, 17033
- Penn State Children's Hospital
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, Estados Unidos, 19107
- Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, Estados Unidos, 19134
- Saint Christopher's Hospital for Children
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- UPMC Hillman Cancer Center
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Pittsburgh, Pennsylvania, Estados Unidos, 15224
- Children's Hospital of Pittsburgh of UPMC
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29425
- Medical University of South Carolina
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Columbia, South Carolina, Estados Unidos, 29203
- Prisma Health Richland Hospital
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Gaffney, South Carolina, Estados Unidos, 29341
- Gibbs Cancer Center-Gaffney
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Greenville, South Carolina, Estados Unidos, 29607
- Saint Francis Cancer Center
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Greenville, South Carolina, Estados Unidos, 29601
- Saint Francis Hospital
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Greenville, South Carolina, Estados Unidos, 29605
- BI-LO Charities Children's Cancer Center
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Greer, South Carolina, Estados Unidos, 29651
- Gibbs Cancer Center-Pelham
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Spartanburg, South Carolina, Estados Unidos, 29303
- Spartanburg Medical Center
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South Dakota
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Sioux Falls, South Dakota, Estados Unidos, 57117-5134
- Sanford USD Medical Center - Sioux Falls
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Tennessee
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Knoxville, Tennessee, Estados Unidos, 37916
- East Tennessee Childrens Hospital
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Memphis, Tennessee, Estados Unidos, 38105
- Saint Jude Children's Research Hospital
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Nashville, Tennessee, Estados Unidos, 37232
- Vanderbilt University/Ingram Cancer Center
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Nashville, Tennessee, Estados Unidos, 37203
- The Children's Hospital at TriStar Centennial
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Texas
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Austin, Texas, Estados Unidos, 78723
- Dell Children's Medical Center of Central Texas
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Corpus Christi, Texas, Estados Unidos, 78411
- Driscoll Children's Hospital
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Dallas, Texas, Estados Unidos, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Dallas, Texas, Estados Unidos, 75230
- Medical City Dallas Hospital
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El Paso, Texas, Estados Unidos, 79905
- El Paso Children's Hospital
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Fort Worth, Texas, Estados Unidos, 76104
- Cook Children's Medical Center
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Houston, Texas, Estados Unidos, 77030
- UT MD Anderson Cancer Center
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Houston, Texas, Estados Unidos, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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Lubbock, Texas, Estados Unidos, 79410
- Covenant Children's Hospital
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Lubbock, Texas, Estados Unidos, 79415
- UMC Cancer Center / UMC Health System
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San Antonio, Texas, Estados Unidos, 78229
- University of Texas Health Science Center at San Antonio
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San Antonio, Texas, Estados Unidos, 78207
- Children's Hospital of San Antonio
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San Antonio, Texas, Estados Unidos, 78229
- Methodist Children's Hospital of South Texas
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Temple, Texas, Estados Unidos, 76508
- Scott and White Memorial Hospital
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Utah
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Salt Lake City, Utah, Estados Unidos, 84113
- Primary Children's Hospital
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Virginia
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Charlottesville, Virginia, Estados Unidos, 22908
- University of Virginia Cancer Center
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Norfolk, Virginia, Estados Unidos, 23507
- Children's Hospital of The King's Daughters
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Richmond, Virginia, Estados Unidos, 23235
- VCU Massey Cancer Center at Stony Point
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Richmond, Virginia, Estados Unidos, 23298
- VCU Massey Comprehensive Cancer Center
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Seattle Children's Hospital
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Spokane, Washington, Estados Unidos, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
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Tacoma, Washington, Estados Unidos, 98405
- Mary Bridge Children's Hospital and Health Center
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Tacoma, Washington, Estados Unidos, 98431
- Madigan Army Medical Center
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West Virginia
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Charleston, West Virginia, Estados Unidos, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
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Wisconsin
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Green Bay, Wisconsin, Estados Unidos, 54301
- Saint Vincent Hospital Cancer Center Green Bay
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Madison, Wisconsin, Estados Unidos, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Marshfield, Wisconsin, Estados Unidos, 54449
- Marshfield Medical Center-Marshfield
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Children's Hospital of Wisconsin
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Christchurch, Nova Zelândia, 8011
- Christchurch Hospital
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Auckland
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Grafton, Auckland, Nova Zelândia, 1145
- Starship Children's Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Patients must be < 40 years of age at the time of enrollment.
- Patients must have a body surface area of >= 0.8 m^2 at the time of enrollment.
- Patients must have histologic diagnosis (by institutional pathologist) of newly diagnosed high grade osteosarcoma. Primary tumors of all extremity and axial sites are eligible as long as diagnosis of high-grade osteosarcoma is established. Osteosarcoma as a second malignancy is eligible if no prior exposure to systemic chemotherapies.
- Feasibility Phase (NOTE: as of Amendment #2B, the feasibility phase has been completed) Patients must have metastatic disease and a resectable primary tumor. Designation of a primary tumor as resectable will be determined at the time of diagnosis by the institutional multidisciplinary team.
For this study, metastatic disease is defined as one or more of the following:
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Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases.
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Lung metastases: defined as biopsy-proven metastasis or the presence of one or more pulmonary lesions >= 5 mm, OR multiple pulmonary lesions >= 3 mm or greater in size.
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Bone metastases: Areas suspicious for bone metastasis based on fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET) scan (or whole body technetium-99 bone scan if 18F-FDG-PET is unavailable at the treating institution) require confirmatory biopsy or supportive anatomic imaging of at least one suspicious site with either magnetic resonance imaging (MRI) or computed tomography (CT) (whole body 18F-FDG-PET/CT or 18F-FDG-PET/MR scans are acceptable).
- Efficacy Phases (Phase 2/3) NOTE: as of Amendment #2B, the efficacy phase is open for enrollment.
Patients with both localized and metastatic disease are eligible for the efficacy phase, regardless of resectability. Patients will be enrolled to two separate cohorts:
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Cohort 1 (Standard Risk): Patients with non-pelvic primary osteosarcoma deemed to be resectable at the time of diagnosis by the institutional multidisciplinary team, without evidence of metastatic lesions.
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Cohort 2 (High-Risk): Patients with a primary pelvic tumor, a primary tumor designated as unresectable by the institutional multidisciplinary team, AND/OR radiographic evidence of metastatic lesions.
- A serum creatinine based on age/sex as follows (within 7 days prior to enrollment unless otherwise indicated):
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(Age: Maximum Serum Creatinine [mg/dL]; Sex)
- 1 month to < 6 months: 0.4 (male); 0.4 (female)
- 6 months to < 1 year: 0.5 (male); 0.5 (female)
- 1 to < 2 years: 0.6 (male); 0.6 (female)
- 2 to < 6 years: 0.8 (male); 0.8 (female)
- 6 to < 10 years: 1 (male); 1 (female)
- 10 to < 13 years: 1.2 (male); 1.2 (female)
- 13 to < 16 years: 1.5 (male); 1.4 (female)
- >= 16 years: 1.7 (male); 1.4 (female)
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OR - a 24 hour urine creatinine clearance >= 70 mL/min/1.73 m^2
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OR - a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
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Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment unless otherwise indicated)
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment unless otherwise indicated)
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Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
- No history of congenital prolonged corrected QT (QTc) syndrome, New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias
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Shortening fraction of >= 27%, or
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Ejection fraction of >= 50%
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Corrected QT interval by Fridericia (QTcF) < 480 msec on electrocardiogram. Patients with Grade 1 prolonged QTc (450-480 msec) at time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications).
- Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment unless otherwise indicated)
- Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment) (within 7 days prior to enrollment unless otherwise indicated)
- Hemoglobin >= 8.0 g/dL (within 7 days prior to enrollment unless otherwise indicated)
- International normalized ratio (INR) =< 1.5 (within 7 days prior to enrollment unless otherwise indicated)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4, CYP2D6, and/or MRP2 transporter protein.
- All patients and/or their parents or legal guardians must sign a written informed consent.
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
- Patients who have received previous systemic therapy for osteosarcoma or a prior oncologic diagnosis.
- Patients who have central nervous system metastases.
- Patients with central cavitating pulmonary lesions invading or encasing any major blood vessels in the lung.
- Patients who are unable to swallow tablets. Tablets cannot be crushed or chewed.
- Patients with gastrointestinal disorders including active disorders associated with a high risk of perforation or fistula formation. Specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, bowel obstruction, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment.
- Patients with active bleeding or bleeding diathesis. No clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding within 3 months prior to enrollment.
- Patients with uncompensated or symptomatic hypothyroidism. Patients who have hypothyroidism controlled with thyroid replacement hormone are eligible.
- Patients with moderate to severe hepatic impairment (Child-Pugh B or C).
- Patients who have had primary tumor resection or attempted curative resection of metastases prior to enrollment.
- Patients who have undergone other major surgical procedure (eg, laparotomy) within 14 days prior to enrollment. Thoracoscopic procedures for diagnostic purposes (biopsy of lung nodule) and central access such as port-a-cath placement are allowed.
- Patients with a history of serious or non-healing wound or bone fracture (pathologic fracture of primary tumor is not considered exclusion).
- Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of cabozantinib.
- Patients with previously identify allergy or hypersensitivity to components of the study treatment formulations.
- Patients who are receiving any other investigational agent not defined within this protocol are not eligible.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
- Patients who received enzyme-inducing anticonvulsants within 14 days prior to enrollment.
- Patients with a prior history of hypertension (> 95th percentile for age, height, and sex for patients < 18 years and > 140/90 mmHg for patients >= 18 years requiring medication for blood pressure control.
- Patients who are receiving drugs that prolong QTc.
- Patients receiving anticoagulation with oral coumarin agents (eg warfarin), direct thrombin inhibitors (eg dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (eg, clopidogrel). Low dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH and direct factor Xa inhibitors rivaroxaban or apixaban are allowed in subjects who are on a stable dose for at least 6 weeks before the first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
- Patients receiving strong CYP3A4 inducers or strong CYP3A4 inhibitors.
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of protocol therapy.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador Ativo: Efficacy Phase Arm A (MAP)
Standard risk patients receive methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study. |
Given IV
Outros nomes:
Given IV
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Given IV
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Undergo CT
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Undergo MRI
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Undergo surgery
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Undergo bone scintography
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Undergo X-ray
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Experimental: Efficacy Phase Arm B (cabozantinib, MAP)
Standard risk patients receive cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive one 35-day "consolidation" cycle with methotrexate IV, doxorubicin IV, and cisplatin IV, then a second 35-day "consolidation" cycle with cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV, followed by two additional 35-day "consolidation" cycles with cabozantinib PO, methotrexate IV, and doxorubicin IV. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study. |
Given IV
Outros nomes:
Given IV
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Given IV
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Undergo CT
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Undergo MRI
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Given PO
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Undergo surgery
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Undergo bone scintography
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Undergo X-ray
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Comparador Ativo: Efficacy Phase Arm C (MAP)
High risk patients receive methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study. |
Given IV
Outros nomes:
Given IV
Outros nomes:
Given IV
Outros nomes:
Undergo CT
Outros nomes:
Undergo MRI
Outros nomes:
Undergo surgery
Outros nomes:
Undergo bone scintography
Outros nomes:
Undergo X-ray
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Experimental: Efficacy Phase Arm D (cabozantinib, MAP)
High risk patients receive cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive one 35-day "consolidation" cycle with methotrexate IV, doxorubicin IV, and cisplatin IV, then a second 35-day "consolidation" cycle with cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV, followed by two additional 35-day "consolidation" cycles with cabozantinib PO, methotrexate IV, and doxorubicin IV. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study. |
Given IV
Outros nomes:
Given IV
Outros nomes:
Given IV
Outros nomes:
Undergo CT
Outros nomes:
Undergo MRI
Outros nomes:
Given PO
Outros nomes:
Undergo bone scintography
Outros nomes:
Undergo X-ray
Outros nomes:
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Experimental: Feasibility phase (cabozantinib, MAP)
(CLOSED TO ACCRUAL 05/09/2025): Patients receive cabozantinib orally (PO), methotrexate intravenously (IV), doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles. Patients are then considered for appropriate local control. Then they receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle, followed by cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle, and cabozantinib PO, methotrexate IV, and doxorubicin IV for two 35-day cycles. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles. |
Given IV
Outros nomes:
Given IV
Outros nomes:
Given IV
Outros nomes:
Undergo CT
Outros nomes:
Undergo MRI
Outros nomes:
Given PO
Outros nomes:
Undergo surgery
Outros nomes:
Undergo bone scintography
Outros nomes:
Undergo X-ray
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Occurrence of dose-limiting toxicity (Feasibility)
Prazo: Baseline up to 6 weeks
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Only patients with high risk osteosarcoma who have a primary tumor considered resectable at the time of enrollment will be enrolled to this part of the trial. If a feasible dose cannot be established, the study committee will consult with Children's Oncology Group leadership and National Cancer Institute Cancer Therapy Evaluation Program regarding possible modifications of the regimen and subsequent protocol amendment. |
Baseline up to 6 weeks
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Event-free survival (EFS) (Phase II)
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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The randomization and analysis will be stratified according to risk group. An assessment of the reduction in risk for EFS-event at the designated landmark time will be used to determine whether the trial continues to part 3. If the study proceeds to part 3, patients enrolled to part 2 of the trial will contribute to the primary analyses for part 3 of the study. If the interim criterion for continuation is not obtained, accrual will be closed with the conclusion that cabozantinib does not reduce sufficiently the risk for EFS-event for patients with newly-diagnosed osteosarcoma. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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EFS (Phase III)
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will consist of two randomized phase 3 sub-studies ('Phase 3'). One will be conducted in standard risk patients and one will be conducted in high risk patients. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Overall survival
Prazo: From randomization until death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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The one-sided logrank test will be the primary statistical methodology for assessing the null statistical hypothesis. The assessment of the reduction in risk of EFS-event will be conducted in standard risk patients and high risk patients separately. |
From randomization until death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will validate whether elevated circulating tumor deoxyribonucleic acid (ctDNA) levels greater than or equal to 5% at the time of diagnosis are associated with increased risk of EFS-event in patients with localized, resectable osteosarcoma. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will validate whether elevated ctDNA levels greater than or equal to 5% at the time of diagnosis are associated with increased risk of EFS-event in patients with metastatic, pelvic and unresectable osteosarcoma. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will validate whether elevated ctDNA levels greater than or equal to 3% after initiation of therapy and prior to definitive surgery are associated with increased risk of EFS-event in patients with localized, resectable osteosarcoma. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will validate whether elevated ctDNA levels greater than or equal to 3% after initiation of therapy and prior to definitive surgery are associated with increased risk of EFS-event in patients with metastatic, pelvic and unresectable osteosarcoma. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Change in symptom burden and tolerability
Prazo: Up to 5 years after completion of study treatment
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Will determine whether methotrexate, doxorubicin, and cisplatin (MAP) chemotherapy plus cabozantinib results in increased symptom burden and decreased tolerability to patients as measured by patient reported therapy-specific acute toxicities (Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events [PRO-CTCAE]). |
Up to 5 years after completion of study treatment
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will determine whether ctDNA at diagnosis and early on-treatment, as a continuous measurement of ctDNA burden, is associated with an increased risk of EFS-event in patients with newly diagnosed osteosarcoma. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will evaluate whether the magnitude of change in ctDNA levels from diagnosis to planned surgical procedure is associated with risk of EFS-event in patients with newly diagnosed osteosarcoma. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will determine whether ctDNA levels greater than or equal to 3% after planned surgical procedures are associated with increased risk of EFS-event. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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Will describe the presence of specific copy-number alterations, including MYC amplifications, detected in ctDNA and matched diagnostic tumor samples in patients with newly diagnosed osteosarcoma and determine whether frequently occurring copy-number alterations are associated with increased risk of EFS-event. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment
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ctDNA burden
Prazo: Up to 5 years after completion of study treatment
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Will determine whether ctDNA burden is predictive of response to the experimental therapy in patients with newly diagnosed osteosarcoma. |
Up to 5 years after completion of study treatment
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Impact of combination therapy on symptom bother
Prazo: Up to 5 years after completion of study treatment
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Will prospectively compare the impact of combination therapy on symptom bother as measured by the Functional Assessment of Cancer Therapy-General Questionnaire item GP5 in patients with osteosarcoma receiving MAP chemotherapy with or without cabozantinib, and to assess the relationship between symptom bother and number of patient-reported acute toxicities (as measured by the PRO-CTCAE). |
Up to 5 years after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 1 year after completion of study treatment
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Estimates of 1-year EFS for standard risk (SR) and high risk (HR) patients on each Arm MAP and Arm cabozantinib (CABO)-MAP and the corresponding 95% confidence intervals (CIs) by sex. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 1 year after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 1 year after completion of study treatment
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Estimates of 1-year EFS for SR and HR patients on each Arm MAP and Arm CABO-MAP and the corresponding 95% CIs by race. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 1 year after completion of study treatment
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EFS
Prazo: From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 1 year after completion of study treatment
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Estimates of 1-year EFS for SR and HR patients on each Arm MAP and Arm CABO-MAP and the corresponding 95% CIs by ethnicity. |
From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 1 year after completion of study treatment
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Michael W Bishop, Children's Oncology Group
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Neoplasias
- Neoplasias por Tipo Histológico
- Sarcoma
- Neoplasias de Tecidos Conjuntivos e Moles
- Neoplasias, Tecido Ósseo
- Neoplasias do Tecido Conjuntivo
- Osteossarcoma
- Produtos químicos orgânicos
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Técnicas de investigação
- Hidrocarbonetos
- Hidrocarbonetos, cíclicos
- Carboidratos
- Fenômenos físicos
- Hidrocarbonetos aromáticos policíclicos
- Hidrocarbonetos, aromáticos
- Compostos policíclicos
- Glicosídeos
- Equipamentos e suprimentos
- Produtos químicos inorgânicos
- Compostos de cloro
- Compostos de nitrogênio
- Elementos
- Metais
- Técnicas de química, analíticas
- Análise de espectro
- Pterins
- Pteridinas
- Metais, pesados
- Aminopterina
- Antraciclinas
- Nafthacenos
- Aminoglicosídeos
- Compostos de platina
- Fenômenos eletromagnéticos
- Fenômenos magnéticos
- Daunorubicina
- Elementos de transição
- Radiação eletromagnética
- Radiação
- Radiação, ionizando
- Metotrexato
- Doxorrubicina
- Cisplatina
- Citrato de 1,2-diaminociclohexanoplatina II
- Espectroscopia de ressonância magnética
- Procedimentos cirúrgicos, operatórios
- Platina
- Raios X
- Cabozantinib
- Merphos
- Fantasmas, imagem
Outros números de identificação do estudo
- NCI-2022-08567
- U10CA180886 (Concessão/Contrato do NIH dos EUA)
- AOST2032 (Outro identificador: CTEP)
- NCI-2022-08567 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- AOST2032 (Outro identificador: Children's Oncology Group)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
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Informações sobre medicamentos e dispositivos, documentos de estudo
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