Test af Olaparib og Temozolomid versus den sædvanlige behandling for livmoderleiomyosarkom efter kemoterapi er holdt op med at virke
Et randomiseret fase 2/3-studie af Olaparib Plus Temozolomid versus Investigator's Choice til behandling af patienter med avanceret uterin leiomyosarkom efter progression på tidligere kemoterapi
This phase II/III trial compares the effect of the combination treatment with olaparib and temozolomide to trabectedin or pazopanib (two of the most common chemotherapy drugs used as usual approach) in patients with uterine leiomyosarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) after initial chemotherapy has stopped working. The usual approach is defined as care most people get for advanced uterine leiomyosarcoma. Olaparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Temozolomide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. The combination of olaparib and temozolomide may work better than the usual treatment in shrinking or stabilizing advanced uterine leiomyosarcoma after initial chemotherapy has stopped working.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
PRIMARY OBJECTIVES:
I. To compare the progression free survival (PFS) of olaparib plus temozolomide (Arm 1) as compared to investigator's choice (trabectedin or pazopanib hydrochloride [pazopanib]) (Arm 2) for the treatment of patients with advanced uterine leiomyosarcoma (uLMS) who have received two or more prior lines of therapy as determined by investigator (local site) assessment. (Phase 2) II. To compare the overall survival (OS) of olaparib plus temozolomide (Arm 1) as compared to investigator's choice (trabectedin or pazopanib) (Arm 2) for the treatment of patients with advanced uLMS who have received two or more prior lines of therapy. (Phase 3)
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of each treatment by determining adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 5 and patient-reported toxicity using Patient-Reported Outcome (PRO)-CTCAE version 1 in and across each treatment arm. (Phase 2/3) II. To evaluate the objective response rate (ORR), duration of response (DOR) and disease control rate (DCR) in and across each treatment arm as determined by investigator assessment. (Phase 2/3)
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 of each cycle and olaparib PO twice daily (BID) on days 1-7 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and/or bone scans throughout the trial. Patients also undergo collection of blood samples throughout the trial.
ARM 2: Patients receive trabectedin intravenously (IV) continuously over 24 hours on day 1 of each cycle or pazopanib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo transthoracic echocardiography (TTE) or multi-gated acquisition scan (MUGA) on study and as clinically indicated, as well as collection of blood samples throughout the trial.
After completion of study treatment, patients without disease progression are followed every 6 weeks until disease progression. After disease progression, patients are followed every 3 months for the first 2 years, then every 6 months thereafter until 5 years post-randomization or death, whichever comes first.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 2
- Fase 3
Kontakter og lokationer
Studiesteder
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Alabama
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Birmingham, Alabama, Forenede Stater, 35233
- University of Alabama at Birmingham Cancer Center
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Alaska
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Anchorage, Alaska, Forenede Stater, 99508
- Alaska Women's Cancer Care
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Arizona
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Phoenix, Arizona, Forenede Stater, 85054
- Mayo Clinic Hospital in Arizona
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California
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Duarte, California, Forenede Stater, 91010
- City of Hope Comprehensive Cancer Center
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Dublin, California, Forenede Stater, 94568
- Epic Care-Dublin
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Emeryville, California, Forenede Stater, 94608
- Epic Care Partners in Cancer Care
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Irvine, California, Forenede Stater, 92618
- City of Hope at Irvine Lennar
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Martinez, California, Forenede Stater, 94553-3156
- Contra Costa Regional Medical Center
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Walnut Creek, California, Forenede Stater, 94597
- Epic Care Cyberknife Center
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- UCHealth University of Colorado Hospital
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Colorado Springs, Colorado, Forenede Stater, 80909
- UCHealth Memorial Hospital Central
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Colorado Springs, Colorado, Forenede Stater, 80920
- Memorial Hospital North
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Fort Collins, Colorado, Forenede Stater, 80524
- Poudre Valley Hospital
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Fort Collins, Colorado, Forenede Stater, 80528
- Cancer Care and Hematology-Fort Collins
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Greeley, Colorado, Forenede Stater, 80631
- UCHealth Greeley Hospital
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Loveland, Colorado, Forenede Stater, 80538
- Medical Center of the Rockies
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Connecticut
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Derby, Connecticut, Forenede Stater, 06418
- Smilow Cancer Hospital-Derby Care Center
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Fairfield, Connecticut, Forenede Stater, 06824
- Smilow Cancer Hospital Care Center-Fairfield
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Glastonbury, Connecticut, Forenede Stater, 06033
- Smilow Cancer Hospital Care Center at Glastonbury
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Greenwich, Connecticut, Forenede Stater, 06830
- Smilow Cancer Hospital Care Center at Greenwich
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Guilford, Connecticut, Forenede Stater, 06437
- Smilow Cancer Hospital Care Center - Guilford
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Hartford, Connecticut, Forenede Stater, 06105
- Smilow Cancer Hospital Care Center at Saint Francis
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New Haven, Connecticut, Forenede Stater, 06520
- Yale University
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North Haven, Connecticut, Forenede Stater, 06473
- Yale-New Haven Hospital North Haven Medical Center
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Stamford, Connecticut, Forenede Stater, 06902
- Smilow Cancer Hospital Care Center at Long Ridge
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Torrington, Connecticut, Forenede Stater, 06790
- Smilow Cancer Hospital-Torrington Care Center
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Trumbull, Connecticut, Forenede Stater, 06611
- Smilow Cancer Hospital Care Center-Trumbull
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Waterbury, Connecticut, Forenede Stater, 06708
- Smilow Cancer Hospital-Waterbury Care Center
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Waterford, Connecticut, Forenede Stater, 06385
- Smilow Cancer Hospital Care Center - Waterford
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District of Columbia
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Washington D.C., District of Columbia, Forenede Stater, 20010
- MedStar Washington Hospital Center
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Florida
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Deerfield Beach, Florida, Forenede Stater, 33442
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Jacksonville, Florida, Forenede Stater, 32224-9980
- Mayo Clinic in Florida
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Miami, Florida, Forenede Stater, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Plantation, Florida, Forenede Stater, 33324
- UM Sylvester Comprehensive Cancer Center at Plantation
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Georgia
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Savannah, Georgia, Forenede Stater, 31405
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
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Idaho
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Boise, Idaho, Forenede Stater, 83712
- Saint Luke's Cancer Institute - Boise
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Fruitland, Idaho, Forenede Stater, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, Forenede Stater, 83642
- Saint Luke's Cancer Institute - Meridian
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Nampa, Idaho, Forenede Stater, 83687
- Saint Luke's Cancer Institute - Nampa
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Twin Falls, Idaho, Forenede Stater, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Chicago, Illinois, Forenede Stater, 60611
- Northwestern University
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Chicago, Illinois, Forenede Stater, 60612
- University of Illinois
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Danville, Illinois, Forenede Stater, 61832
- Carle at The Riverfront
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DeKalb, Illinois, Forenede Stater, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Effingham, Illinois, Forenede Stater, 62401
- Carle Physician Group-Effingham
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Evanston, Illinois, Forenede Stater, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Geneva, Illinois, Forenede Stater, 60134
- Northwestern Medicine Cancer Center Delnor
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Glenview, Illinois, Forenede Stater, 60026
- NorthShore University HealthSystem-Glenbrook Hospital
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Highland Park, Illinois, Forenede Stater, 60035
- NorthShore University HealthSystem-Highland Park Hospital
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Lake Forest, Illinois, Forenede Stater, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, Forenede Stater, 61938
- Carle Physician Group-Mattoon/Charleston
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Urbana, Illinois, Forenede Stater, 61801
- Carle Cancer Center
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Warrenville, Illinois, Forenede Stater, 60555
- Northwestern Medicine Cancer Center Warrenville
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Iowa
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Ames, Iowa, Forenede Stater, 50010
- Mary Greeley Medical Center
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Ames, Iowa, Forenede Stater, 50010
- McFarland Clinic - Ames
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Boone, Iowa, Forenede Stater, 50036
- McFarland Clinic - Boone
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Council Bluffs, Iowa, Forenede Stater, 51503
- Heartland Oncology and Hematology LLP
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Des Moines, Iowa, Forenede Stater, 50314
- Mercy Medical Center - Des Moines
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Fort Dodge, Iowa, Forenede Stater, 50501
- McFarland Clinic - Trinity Cancer Center
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Iowa City, Iowa, Forenede Stater, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Jefferson, Iowa, Forenede Stater, 50129
- McFarland Clinic - Jefferson
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Marshalltown, Iowa, Forenede Stater, 50158
- McFarland Clinic - Marshalltown
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Kentucky
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Lexington, Kentucky, Forenede Stater, 40503
- Baptist Health Lexington
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Louisiana
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Baton Rouge, Louisiana, Forenede Stater, 70817
- Our Lady of the Lake Medical Oncology
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New Orleans, Louisiana, Forenede Stater, 70112
- University Medical Center New Orleans
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Maine
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Scarborough, Maine, Forenede Stater, 04074
- MaineHealth Maine Medical Center- Scarborough
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan Rogel Cancer Center
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Battle Creek, Michigan, Forenede Stater, 49017
- Bronson Battle Creek
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Grand Rapids, Michigan, Forenede Stater, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, Forenede Stater, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, Forenede Stater, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Forenede Stater, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Forenede Stater, 49009
- Beacon Kalamazoo Cancer Center
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Muskegon, Michigan, Forenede Stater, 49444
- Trinity Health Muskegon Hospital
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Norton Shores, Michigan, Forenede Stater, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Reed City, Michigan, Forenede Stater, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, Forenede Stater, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Traverse City, Michigan, Forenede Stater, 49684
- Munson Medical Center
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Wyoming, Michigan, Forenede Stater, 49519
- University of Michigan Health - West
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Minnesota
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Coon Rapids, Minnesota, Forenede Stater, 55433
- Mercy Hospital
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Edina, Minnesota, Forenede Stater, 55435
- Fairview Southdale Hospital
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Minneapolis, Minnesota, Forenede Stater, 55407
- Abbott-Northwestern Hospital
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic in Rochester
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Saint Louis Park, Minnesota, Forenede Stater, 55416
- Park Nicollet Clinic - Saint Louis Park
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Saint Paul, Minnesota, Forenede Stater, 55101
- Regions Hospital
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Saint Paul, Minnesota, Forenede Stater, 55102
- United Hospital
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Missouri
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Creve Coeur, Missouri, Forenede Stater, 63141
- Siteman Cancer Center at West County Hospital
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St Louis, Missouri, Forenede Stater, 63110
- Washington University School of Medicine
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St Louis, Missouri, Forenede Stater, 63129
- Siteman Cancer Center-South County
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St Louis, Missouri, Forenede Stater, 63141
- Mercy Hospital Saint Louis
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Nebraska
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Omaha, Nebraska, Forenede Stater, 68114
- Nebraska Methodist Hospital
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Omaha, Nebraska, Forenede Stater, 68114
- Oncology Associates PC
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Omaha, Nebraska, Forenede Stater, 68114
- Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
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New Jersey
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Basking Ridge, New Jersey, Forenede Stater, 07920
- Memorial Sloan Kettering Basking Ridge
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Middletown, New Jersey, Forenede Stater, 07748
- Memorial Sloan Kettering Monmouth
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Montvale, New Jersey, Forenede Stater, 07645
- Memorial Sloan Kettering Bergen
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New York
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Buffalo, New York, Forenede Stater, 14263
- Roswell Park Cancer Institute
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Commack, New York, Forenede Stater, 11725
- Memorial Sloan Kettering Commack
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Harrison, New York, Forenede Stater, 10604
- Memorial Sloan Kettering Westchester
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Lake Success, New York, Forenede Stater, 11042
- Northwell Health/Center for Advanced Medicine
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New York, New York, Forenede Stater, 10065
- Memorial Sloan Kettering Cancer Center
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Uniondale, New York, Forenede Stater, 11553
- Memorial Sloan Kettering Nassau
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North Carolina
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Chapel Hill, North Carolina, Forenede Stater, 27599
- UNC Lineberger Comprehensive Cancer Center
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Durham, North Carolina, Forenede Stater, 27710
- Duke University Medical Center
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Greenville, North Carolina, Forenede Stater, 27834
- ECU Health Medical Center
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Ohio
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Avon, Ohio, Forenede Stater, 44011
- UH Seidman Cancer Center at UH Avon Health Center
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Beachwood, Ohio, Forenede Stater, 44122
- UHHS-Chagrin Highlands Medical Center
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Cleveland, Ohio, Forenede Stater, 44106
- Case Western Reserve University
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Cleveland, Ohio, Forenede Stater, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, Forenede Stater, 44111
- Cleveland Clinic Cancer Center/Fairview Hospital
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Mayfield Heights, Ohio, Forenede Stater, 44124
- Hillcrest Hospital Cancer Center
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Clackamas, Oregon, Forenede Stater, 97015
- Clackamas Radiation Oncology Center
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Gresham, Oregon, Forenede Stater, 97030
- Legacy Mount Hood Medical Center
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Newberg, Oregon, Forenede Stater, 97132
- Providence Newberg Medical Center
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Oregon City, Oregon, Forenede Stater, 97045
- Providence Willamette Falls Medical Center
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Portland, Oregon, Forenede Stater, 97239
- Oregon Health and Science University
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Portland, Oregon, Forenede Stater, 97210
- Legacy Good Samaritan Hospital and Medical Center
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Portland, Oregon, Forenede Stater, 97213
- Providence Portland Medical Center
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Portland, Oregon, Forenede Stater, 97225
- Providence Saint Vincent Medical Center
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Tualatin, Oregon, Forenede Stater, 97062
- Legacy Meridian Park Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19111
- Fox Chase Cancer Center
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Philadelphia, Pennsylvania, Forenede Stater, 19107
- Thomas Jefferson University Hospital
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Willow Grove, Pennsylvania, Forenede Stater, 19090
- Asplundh Cancer Pavilion
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Rhode Island
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Providence, Rhode Island, Forenede Stater, 02905
- Women and Infants Hospital
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Westerly, Rhode Island, Forenede Stater, 02891
- Smilow Cancer Hospital Care Center - Westerly
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South Carolina
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Bluffton, South Carolina, Forenede Stater, 29910
- Saint Joseph's/Candler - Bluffton Campus
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Charleston, South Carolina, Forenede Stater, 29425
- Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37232
- Vanderbilt University/Ingram Cancer Center
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Virginia
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Richmond, Virginia, Forenede Stater, 23235
- VCU Massey Cancer Center at Stony Point
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Richmond, Virginia, Forenede Stater, 23298
- VCU Massey Comprehensive Cancer Center
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Washington
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Seattle, Washington, Forenede Stater, 98195
- University of Washington Medical Center - Montlake
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Seattle, Washington, Forenede Stater, 98109
- Fred Hutchinson Cancer Center
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Vancouver, Washington, Forenede Stater, 98686
- Legacy Salmon Creek Hospital
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Vancouver, Washington, Forenede Stater, 98684
- Legacy Cancer Institute Medical Oncology and Day Treatment
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West Virginia
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Charleston, West Virginia, Forenede Stater, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
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Wisconsin
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Eau Claire, Wisconsin, Forenede Stater, 54701
- Marshfield Medical Center-EC Cancer Center
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Marshfield, Wisconsin, Forenede Stater, 54449
- Marshfield Medical Center-Marshfield
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Milwaukee, Wisconsin, Forenede Stater, 53226
- Medical College of Wisconsin
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Minocqua, Wisconsin, Forenede Stater, 54548
- Marshfield Medical Center - Minocqua
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Rice Lake, Wisconsin, Forenede Stater, 54868
- Marshfield Medical Center-Rice Lake
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Stevens Point, Wisconsin, Forenede Stater, 54482
- Marshfield Medical Center-River Region at Stevens Point
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Weston, Wisconsin, Forenede Stater, 54476
- Marshfield Medical Center - Weston
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San Juan, Puerto Rico, 00927
- Centro Comprensivo de Cancer de UPR
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
-
Histologically confirmed leiomyosarcoma of uterine origin, as established by the site institutional practice for pathology confirmation for research studies when enrolling the patient on study. Central pathology review will not occur.
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Metastatic or locally advanced and surgically unresectable disease, in the opinion of the treating investigator.
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Patients must have at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria to be eligible for the study.
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Not pregnant and not nursing, because this study involves agents that have known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
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Age >= 18 years.
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Eastern Cooperative Oncology Group (ECOG) Performance Status =< 2.
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Patients must have had prior progression on, or intolerance to, at least two prior lines of systemic therapy for advanced uLMS, one of which was an anthracycline (anthracycline monotherapy or combination). Adjuvant chemotherapy will qualify as a prior line of treatment. Endocrine treatment will not qualify as a prior line of treatment.
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Patients may not have received prior treatment with any PARP inhibitor, temozolomide or dacarbazine (IV analogue of temozolomide).
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Patients may not have had prior treatment with BOTH of the agents included on the investigator's choice arm: trabectedin AND pazopanib. If the patient has had prior treatment with one of these agents, they are eligible; however, they must be assigned to the other agent for investigator's choice. That is, patients who have received prior pazopanib must be assigned to trabectedin, and patients who have received prior trabectedin must be assigned to pazopanib.
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Patients must have recovered to baseline or =< grade 1 per CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy, with the exception of fatigue (which must be =< grade 2), alopecia and/or endocrinopathies related to prior immunotherapy which are controlled with hormone replacement.
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Patients must have completed all prior anti-cancer treatment, including radiation, >= 28 days prior to registration.
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Patients may have undergone major surgery (related or unrelated to their cancer diagnosis) >= 28 days of registration. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
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Absolute neutrophil count (ANC) >= 1500/mm^3 (within =< 28 days prior to registration).
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Platelet count >= 100,000/mm^3 (within =< 28 days prior to registration).
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Creatinine =< 1.5 * upper limit of normal (ULN) (within =< 28 days prior to registration).
- If creatinine > 1.5 * ULN, then creatinine clearance (CrCl) must be > 50 mL/min, per Cockcroft-Gault method.
-
Hemoglobin >= 9 g/dL (within =< 28 days prior to registration).
- No transfusions =< 14 days before cycle 1 day 1 (C1D1).
-
Total bilirubin =< 1.5 x ULN (within =< 28 days prior to registration).
- If documented Gilbert's: =< 2.0 x ULN.
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Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 3 x ULN (within =< 28 days prior to registration).
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Patients may not have uncontrolled hypertension defined as a blood pressure (BP) > 150/90 on two consecutive assessments during the screening period. If a patient is found to have a BP > 150/90 on two consecutive assessments during the screening period, the patient may be started on an anti-hypertensive regimen, and will be considered eligible if two subsequent measurements are performed and the BP is =< 150/90. If BP is in range on the first measurement, no further measurements are needed.
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Patients must demonstrate a QTcF (Fredericia formula) =< 470 msec on an electrocardiography (EKG) performed during screening. This criterion applies only to patients who will receive pazopanib if randomized to Arm 2. Repeat EKG testing during the screening period is allowed.
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Patients may not have an uncontrolled ventricular arrhythmia or recent (within 3 months) myocardial infarction.
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In addition to the above, patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible, patients should be class 2B or better.
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Patients may not have a history of active or unresolved: perforation, abscess or fistula within 28 days prior to registration (either clinically or radiographically).
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Patients must not have myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or a history of bone marrow biopsy findings at any time consistent with MDS and/or AML.
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For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
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Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
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HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
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Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
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Patients with central nervous system (CNS)/leptomeningeal disease must have undergone definitive treatment, have no evidence of CNS progression on follow-up imaging performed at least 4 weeks after the CNS-directed therapy is completed, and be off all steroids, in order to be eligible.
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Patients must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any other condition that would limit compliance with study requirements.
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Patients must be able to swallow oral medications.
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Patients may not require concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.
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Patients may not require concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
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In order to complete the mandatory patient-completed measure, participants must be able to speak and/or read English and Spanish. Non-English or non-Spanish readers may still participate in the study but are not required to complete the PRO-CTCAE side effect surveys.
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For all patients, prior to randomization and as part of eligibility, the investigator must select the agent which the patient would receive if assigned to the investigator's choice arm, prior to randomization. The patient must meet all eligibility criteria for that agent during screening and prior to randomization.
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Patients without central venous access must be willing to undergo placement of central venous access (i.e. port or peripherally inserted central catheter [PICC] line, per institutional practice) if assigned to the investigator's choice arm and if the investigator intends to treat the patient with trabectedin. The site must be able to place central venous access within 10 days of registration/randomization.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Arm 1 (olaparib, temozolomide)
Patients receive temozolomide PO QD on days 1-7 of each cycle and olaparib PO BID on days 1-7 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo collection of blood samples throughout the trial. |
Undergo MRI
Andre navne:
Given PO
Andre navne:
Undergo MUGA
Andre navne:
Undergo collection of blood samples
Andre navne:
Undergo CT scan
Andre navne:
Given PO
Andre navne:
Undergo bone scan
Andre navne:
Undergo TTE
Andre navne:
|
|
Aktiv komparator: Arm 2 (trabectedin, pazopanib)
Patients receive trabectedin IV continuously over 24 hours on day 1 of each cycle or pazopanib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo TTE or MUGA on study and as clinically indicated, as well as collection of blood samples throughout the trial. |
Undergo MRI
Andre navne:
Undergo MUGA
Andre navne:
Undergo collection of blood samples
Andre navne:
Undergo CT scan
Andre navne:
Undergo bone scan
Andre navne:
Undergo TTE
Andre navne:
Given PO
Andre navne:
Given IV
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Progression Free Survival (PFS) (Phase II)
Tidsramme: Time between the date of randomization and the earliest of disease progression or death, assessed up to 1 year
|
Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms. PFS rates at 1 year will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be assessed as well. |
Time between the date of randomization and the earliest of disease progression or death, assessed up to 1 year
|
|
Overall Survival (OS) (Phase III)
Tidsramme: Time between the date of randomization and the date of death from any cause, assessed up to 5 years
|
Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms. OS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be assessed as well. |
Time between the date of randomization and the date of death from any cause, assessed up to 5 years
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Overall Response Rate
Tidsramme: Up to 5 years
|
Will be estimated by dividing the number of evaluable patients that achieve a confirmed response (partial response [PR] or better) by the total number of evaluable patients. This estimate will be calculated by arm and will also include a 95% confidence interval using the properties of the binomial distribution, and compared between the arms using a chi-square test. |
Up to 5 years
|
|
Duration of Response (DOR)
Tidsramme: Time from first evidence of response until disease progression (or death), assessed up to 5 years
|
This analysis is restricted to those patients that achieved a confirmed response (PR or better). Patients that go off of study treatment prior to progression will have their DOR time censored at that time. |
Time from first evidence of response until disease progression (or death), assessed up to 5 years
|
|
Disease Control Rate
Tidsramme: Up to 6 weeks
|
Will be estimated using the number of patients that achieve complete response, partial response, or stable disease at the 6 week assessment divided by all evaluable patients. This estimate will be calculated by arm and will also include a 95% confidence interval using the properties of the binomial distribution, and compared between the arms using a chi-square test. |
Up to 6 weeks
|
|
Incidence of Adverse Events
Tidsramme: Up to 4 weeks after the end of study treatment
|
Adverse events will be recorded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for each patient. Frequency tables and summary statistics will be used and with the appropriate methods of evaluating categorical and continuous data. In addition, patient reported safety and tolerability will be assessed using Patient-Reported Outcomes (PRO)-CTCAE for a prespecified group of expected toxicities. PRO-CTCAE assessments will occur prior to registration and on day 1 of every cycle during treatment. Collection of PRO-CTCAE will be discontinued after cycle 11. |
Up to 4 weeks after the end of study treatment
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Ledende efterforsker: Matthew Ingham, Alliance for Clinical Trials in Oncology
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Organiske kemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Undersøgelsesteknikker
- Kliniske laboratorieteknikker
- Diagnostiske teknikker og procedurer
- Diagnose
- Azoler
- Dacarbazine
- Triazener
- Imidazoler
- Kemiteknikker, analytisk
- Spektrumanalyse
- Dioxoler
- Tetrahydroisoquinoliner
- Isoquinoliner
- Temozolomid
- Trabectedin
- Håndtering af eksemplar
- Magnetisk resonansspektroskopi
- Olaparib
- Pazopanib
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- NCI-2022-05065
- U10CA180821 (U.S. NIH-bevilling/kontrakt)
- NCI-2022-05065 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- A092104 (Anden identifikator: CTEP)
- A092104 (Anden identifikator: Alliance for Clinical Trials in Oncology)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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