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Testowanie olaparybu i temozolomidu w porównaniu ze zwykłym leczeniem mięśniakomięsaka gładkokomórkowego macicy po tym, jak chemioterapia przestała działać

30 września 2026 zaktualizowane przez: National Cancer Institute (NCI)

Randomizowane badanie fazy 2/3 olaparybu plus temozolomid w porównaniu z wyborem badacza w leczeniu pacjentów z zaawansowanym mięśniakomięsakiem gładkokomórkowym macicy po progresji podczas wcześniejszej chemioterapii

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.

Przegląd badań

Status

Aktywny, nie rekrutujący

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

74

Faza

  • Faza 2
  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Portoryko
      • San Juan, Portoryko, 00927
        • Centro Comprensivo de Cancer de UPR
  • Stany Zjednoczone
    • Alabama
      • Birmingham, Alabama, Stany Zjednoczone, 35233
        • University of Alabama at Birmingham Cancer Center
    • Alaska
      • Anchorage, Alaska, Stany Zjednoczone, 99508
        • Alaska Women's Cancer Care
    • Arizona
      • Phoenix, Arizona, Stany Zjednoczone, 85054
        • Mayo Clinic Hospital in Arizona
    • California
      • Duarte, California, Stany Zjednoczone, 91010
        • City of Hope Comprehensive Cancer Center
      • Dublin, California, Stany Zjednoczone, 94568
        • Epic Care-Dublin
      • Emeryville, California, Stany Zjednoczone, 94608
        • Epic Care Partners in Cancer Care
      • Irvine, California, Stany Zjednoczone, 92618
        • City of Hope at Irvine Lennar
      • Martinez, California, Stany Zjednoczone, 94553-3156
        • Contra Costa Regional Medical Center
      • Walnut Creek, California, Stany Zjednoczone, 94597
        • Epic Care Cyberknife Center
    • Colorado
      • Aurora, Colorado, Stany Zjednoczone, 80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs, Colorado, Stany Zjednoczone, 80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs, Colorado, Stany Zjednoczone, 80920
        • Memorial Hospital North
      • Fort Collins, Colorado, Stany Zjednoczone, 80524
        • Poudre Valley Hospital
      • Fort Collins, Colorado, Stany Zjednoczone, 80528
        • Cancer Care and Hematology-Fort Collins
      • Greeley, Colorado, Stany Zjednoczone, 80631
        • UCHealth Greeley Hospital
      • Loveland, Colorado, Stany Zjednoczone, 80538
        • Medical Center of the Rockies
    • Connecticut
      • Derby, Connecticut, Stany Zjednoczone, 06418
        • Smilow Cancer Hospital-Derby Care Center
      • Fairfield, Connecticut, Stany Zjednoczone, 06824
        • Smilow Cancer Hospital Care Center-Fairfield
      • Glastonbury, Connecticut, Stany Zjednoczone, 06033
        • Smilow Cancer Hospital Care Center at Glastonbury
      • Greenwich, Connecticut, Stany Zjednoczone, 06830
        • Smilow Cancer Hospital Care Center at Greenwich
      • Guilford, Connecticut, Stany Zjednoczone, 06437
        • Smilow Cancer Hospital Care Center - Guilford
      • Hartford, Connecticut, Stany Zjednoczone, 06105
        • Smilow Cancer Hospital Care Center at Saint Francis
      • New Haven, Connecticut, Stany Zjednoczone, 06520
        • Yale University
      • North Haven, Connecticut, Stany Zjednoczone, 06473
        • Yale-New Haven Hospital North Haven Medical Center
      • Stamford, Connecticut, Stany Zjednoczone, 06902
        • Smilow Cancer Hospital Care Center at Long Ridge
      • Torrington, Connecticut, Stany Zjednoczone, 06790
        • Smilow Cancer Hospital-Torrington Care Center
      • Trumbull, Connecticut, Stany Zjednoczone, 06611
        • Smilow Cancer Hospital Care Center-Trumbull
      • Waterbury, Connecticut, Stany Zjednoczone, 06708
        • Smilow Cancer Hospital-Waterbury Care Center
      • Waterford, Connecticut, Stany Zjednoczone, 06385
        • Smilow Cancer Hospital Care Center - Waterford
    • District of Columbia
      • Washington D.C., District of Columbia, Stany Zjednoczone, 20010
        • MedStar Washington Hospital Center
    • Florida
      • Deerfield Beach, Florida, Stany Zjednoczone, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Jacksonville, Florida, Stany Zjednoczone, 32224-9980
        • Mayo Clinic in Florida
      • Miami, Florida, Stany Zjednoczone, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Plantation, Florida, Stany Zjednoczone, 33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
    • Georgia
      • Savannah, Georgia, Stany Zjednoczone, 31405
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Idaho
      • Boise, Idaho, Stany Zjednoczone, 83712
        • Saint Luke's Cancer Institute - Boise
      • Fruitland, Idaho, Stany Zjednoczone, 83619
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, Stany Zjednoczone, 83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, Stany Zjednoczone, 83687
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls, Idaho, Stany Zjednoczone, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Chicago, Illinois, Stany Zjednoczone, 60611
        • Northwestern University
      • Chicago, Illinois, Stany Zjednoczone, 60612
        • University of Illinois
      • Danville, Illinois, Stany Zjednoczone, 61832
        • Carle at The Riverfront
      • DeKalb, Illinois, Stany Zjednoczone, 60115
        • Northwestern Medicine Cancer Center Kishwaukee
      • Effingham, Illinois, Stany Zjednoczone, 62401
        • Carle Physician Group-Effingham
      • Evanston, Illinois, Stany Zjednoczone, 60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Geneva, Illinois, Stany Zjednoczone, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Glenview, Illinois, Stany Zjednoczone, 60026
        • NorthShore University HealthSystem-Glenbrook Hospital
      • Highland Park, Illinois, Stany Zjednoczone, 60035
        • NorthShore University HealthSystem-Highland Park Hospital
      • Lake Forest, Illinois, Stany Zjednoczone, 60045
        • Northwestern Medicine Lake Forest Hospital
      • Mattoon, Illinois, Stany Zjednoczone, 61938
        • Carle Physician Group-Mattoon/Charleston
      • Urbana, Illinois, Stany Zjednoczone, 61801
        • Carle Cancer Center
      • Warrenville, Illinois, Stany Zjednoczone, 60555
        • Northwestern Medicine Cancer Center Warrenville
    • Iowa
      • Ames, Iowa, Stany Zjednoczone, 50010
        • Mary Greeley Medical Center
      • Ames, Iowa, Stany Zjednoczone, 50010
        • McFarland Clinic - Ames
      • Boone, Iowa, Stany Zjednoczone, 50036
        • McFarland Clinic - Boone
      • Council Bluffs, Iowa, Stany Zjednoczone, 51503
        • Heartland Oncology and Hematology LLP
      • Des Moines, Iowa, Stany Zjednoczone, 50314
        • Mercy Medical Center - Des Moines
      • Fort Dodge, Iowa, Stany Zjednoczone, 50501
        • McFarland Clinic - Trinity Cancer Center
      • Iowa City, Iowa, Stany Zjednoczone, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
      • Jefferson, Iowa, Stany Zjednoczone, 50129
        • McFarland Clinic - Jefferson
      • Marshalltown, Iowa, Stany Zjednoczone, 50158
        • McFarland Clinic - Marshalltown
    • Kentucky
      • Lexington, Kentucky, Stany Zjednoczone, 40503
        • Baptist Health Lexington
    • Louisiana
      • Baton Rouge, Louisiana, Stany Zjednoczone, 70817
        • Our Lady of the Lake Medical Oncology
      • New Orleans, Louisiana, Stany Zjednoczone, 70112
        • University Medical Center New Orleans
    • Maine
      • Scarborough, Maine, Stany Zjednoczone, 04074
        • MaineHealth Maine Medical Center- Scarborough
    • Massachusetts
      • Boston, Massachusetts, Stany Zjednoczone, 02215
        • Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, Stany Zjednoczone, 48109
        • University of Michigan Rogel Cancer Center
      • Battle Creek, Michigan, Stany Zjednoczone, 49017
        • Bronson Battle Creek
      • Grand Rapids, Michigan, Stany Zjednoczone, 49503
        • Trinity Health Grand Rapids Hospital
      • Grand Rapids, Michigan, Stany Zjednoczone, 49503
        • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
      • Kalamazoo, Michigan, Stany Zjednoczone, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, Stany Zjednoczone, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, Stany Zjednoczone, 49009
        • Beacon Kalamazoo Cancer Center
      • Muskegon, Michigan, Stany Zjednoczone, 49444
        • Trinity Health Muskegon Hospital
      • Norton Shores, Michigan, Stany Zjednoczone, 49444
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
      • Reed City, Michigan, Stany Zjednoczone, 49677
        • Corewell Health Reed City Hospital
      • Saint Joseph, Michigan, Stany Zjednoczone, 49085
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
      • Traverse City, Michigan, Stany Zjednoczone, 49684
        • Munson Medical Center
      • Wyoming, Michigan, Stany Zjednoczone, 49519
        • University of Michigan Health - West
    • Minnesota
      • Coon Rapids, Minnesota, Stany Zjednoczone, 55433
        • Mercy Hospital
      • Edina, Minnesota, Stany Zjednoczone, 55435
        • Fairview Southdale Hospital
      • Minneapolis, Minnesota, Stany Zjednoczone, 55407
        • Abbott-Northwestern Hospital
      • Rochester, Minnesota, Stany Zjednoczone, 55905
        • Mayo Clinic in Rochester
      • Saint Louis Park, Minnesota, Stany Zjednoczone, 55416
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Paul, Minnesota, Stany Zjednoczone, 55101
        • Regions Hospital
      • Saint Paul, Minnesota, Stany Zjednoczone, 55102
        • United Hospital
    • Missouri
      • Creve Coeur, Missouri, Stany Zjednoczone, 63141
        • Siteman Cancer Center at West County Hospital
      • St Louis, Missouri, Stany Zjednoczone, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, Stany Zjednoczone, 63129
        • Siteman Cancer Center-South County
      • St Louis, Missouri, Stany Zjednoczone, 63141
        • Mercy Hospital Saint Louis
    • Nebraska
      • Omaha, Nebraska, Stany Zjednoczone, 68114
        • Nebraska Methodist Hospital
      • Omaha, Nebraska, Stany Zjednoczone, 68114
        • Oncology Associates PC
      • Omaha, Nebraska, Stany Zjednoczone, 68114
        • Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
    • New Jersey
      • Basking Ridge, New Jersey, Stany Zjednoczone, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Middletown, New Jersey, Stany Zjednoczone, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, Stany Zjednoczone, 07645
        • Memorial Sloan Kettering Bergen
    • New York
      • Buffalo, New York, Stany Zjednoczone, 14263
        • Roswell Park Cancer Institute
      • Commack, New York, Stany Zjednoczone, 11725
        • Memorial Sloan Kettering Commack
      • Harrison, New York, Stany Zjednoczone, 10604
        • Memorial Sloan Kettering Westchester
      • Lake Success, New York, Stany Zjednoczone, 11042
        • Northwell Health/Center for Advanced Medicine
      • New York, New York, Stany Zjednoczone, 10065
        • Memorial Sloan Kettering Cancer Center
      • Uniondale, New York, Stany Zjednoczone, 11553
        • Memorial Sloan Kettering Nassau
    • North Carolina
      • Chapel Hill, North Carolina, Stany Zjednoczone, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Durham, North Carolina, Stany Zjednoczone, 27710
        • Duke University Medical Center
      • Greenville, North Carolina, Stany Zjednoczone, 27834
        • ECU Health Medical Center
    • Ohio
      • Avon, Ohio, Stany Zjednoczone, 44011
        • UH Seidman Cancer Center at UH Avon Health Center
      • Beachwood, Ohio, Stany Zjednoczone, 44122
        • UHHS-Chagrin Highlands Medical Center
      • Cleveland, Ohio, Stany Zjednoczone, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, Stany Zjednoczone, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, Stany Zjednoczone, 44111
        • Cleveland Clinic Cancer Center/Fairview Hospital
      • Mayfield Heights, Ohio, Stany Zjednoczone, 44124
        • Hillcrest Hospital Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, Stany Zjednoczone, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Clackamas, Oregon, Stany Zjednoczone, 97015
        • Clackamas Radiation Oncology Center
      • Gresham, Oregon, Stany Zjednoczone, 97030
        • Legacy Mount Hood Medical Center
      • Newberg, Oregon, Stany Zjednoczone, 97132
        • Providence Newberg Medical Center
      • Oregon City, Oregon, Stany Zjednoczone, 97045
        • Providence Willamette Falls Medical Center
      • Portland, Oregon, Stany Zjednoczone, 97239
        • Oregon Health and Science University
      • Portland, Oregon, Stany Zjednoczone, 97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Portland, Oregon, Stany Zjednoczone, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, Stany Zjednoczone, 97225
        • Providence Saint Vincent Medical Center
      • Tualatin, Oregon, Stany Zjednoczone, 97062
        • Legacy Meridian Park Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stany Zjednoczone, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, Stany Zjednoczone, 19107
        • Thomas Jefferson University Hospital
      • Willow Grove, Pennsylvania, Stany Zjednoczone, 19090
        • Asplundh Cancer Pavilion
    • Rhode Island
      • Providence, Rhode Island, Stany Zjednoczone, 02905
        • Women and Infants Hospital
      • Westerly, Rhode Island, Stany Zjednoczone, 02891
        • Smilow Cancer Hospital Care Center - Westerly
    • South Carolina
      • Bluffton, South Carolina, Stany Zjednoczone, 29910
        • Saint Joseph's/Candler - Bluffton Campus
      • Charleston, South Carolina, Stany Zjednoczone, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, Stany Zjednoczone, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Virginia
      • Richmond, Virginia, Stany Zjednoczone, 23235
        • VCU Massey Cancer Center at Stony Point
      • Richmond, Virginia, Stany Zjednoczone, 23298
        • VCU Massey Comprehensive Cancer Center
    • Washington
      • Seattle, Washington, Stany Zjednoczone, 98195
        • University of Washington Medical Center - Montlake
      • Seattle, Washington, Stany Zjednoczone, 98109
        • Fred Hutchinson Cancer Center
      • Vancouver, Washington, Stany Zjednoczone, 98686
        • Legacy Salmon Creek Hospital
      • Vancouver, Washington, Stany Zjednoczone, 98684
        • Legacy Cancer Institute Medical Oncology and Day Treatment
    • West Virginia
      • Charleston, West Virginia, Stany Zjednoczone, 25304
        • Vandalia Health/CAMC Institute for Academic Medicine
    • Wisconsin
      • Eau Claire, Wisconsin, Stany Zjednoczone, 54701
        • Marshfield Medical Center-EC Cancer Center
      • Marshfield, Wisconsin, Stany Zjednoczone, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, Stany Zjednoczone, 53226
        • Medical College of Wisconsin
      • Minocqua, Wisconsin, Stany Zjednoczone, 54548
        • Marshfield Medical Center - Minocqua
      • Rice Lake, Wisconsin, Stany Zjednoczone, 54868
        • Marshfield Medical Center-Rice Lake
      • Stevens Point, Wisconsin, Stany Zjednoczone, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Weston, Wisconsin, Stany Zjednoczone, 54476
        • Marshfield Medical Center - Weston

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.

  • Metastatic or locally advanced and surgically unresectable disease, in the opinion of the treating investigator.

  • 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.

  • 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

  • Age >= 18 years.

  • Eastern Cooperative Oncology Group (ECOG) Performance Status =< 2.

  • 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.

  • Patients may not have received prior treatment with any PARP inhibitor, temozolomide or dacarbazine (IV analogue of temozolomide).

  • 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.

  • 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.

  • Patients must have completed all prior anti-cancer treatment, including radiation, >= 28 days prior to registration.

  • 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.

  • Absolute neutrophil count (ANC) >= 1500/mm^3 (within =< 28 days prior to registration).

  • Platelet count >= 100,000/mm^3 (within =< 28 days prior to registration).

  • 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.

  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 3 x ULN (within =< 28 days prior to registration).

  • 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.

  • 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.

  • Patients may not have an uncontrolled ventricular arrhythmia or recent (within 3 months) myocardial infarction.

  • 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.

  • Patients may not have a history of active or unresolved: perforation, abscess or fistula within 28 days prior to registration (either clinically or radiographically).

  • 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.

  • For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

  • 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.

  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

  • 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.

  • 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.

  • 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.

  • Patients must be able to swallow oral medications.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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.
Procedura: Magnetic Resonance Imaging

Undergo MRI

Inne nazwy:
  • MRI
  • Rezonans magnetyczny
  • Skanowanie rezonansu magnetycznego
  • Obrazowanie medyczne, rezonans magnetyczny / jądrowy rezonans magnetyczny
  • PAN
  • Obrazowanie MR
  • Obrazowanie NMR
  • NMRI
  • Obrazowanie magnetycznego rezonansu jądrowego
  • Obrazowanie metodą rezonansu magnetycznego (MRI)
  • sMRI
  • Rezonans magnetyczny (zabieg)
  • Strukturalny MRI
Lek: Temozolomide

Given PO

Inne nazwy:
  • Temodara
  • SCH 52365
  • Temodal
  • Temcad
  • Metazolaston
  • RP-46161
  • Temomedak
  • TMZ
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazyno-8-karboksyamid, 3,4-dihydro-3-metylo-4-okso-
  • M&B 39831
  • M i B 39831
  • Gliotem
  • Temizol
Procedura: Multigated Acquisition Scan

Undergo MUGA

Inne nazwy:
  • Skanowanie puli krwi
  • Równoważna angiografia radionuklidów
  • Bramkowane obrazowanie puli krwi
  • MUGA
  • Wentrykulografia radionuklidów
  • RNVG
  • Skanowanie SYMA
  • Zsynchronizowane skanowanie akwizycji z wieloma bramkami
  • Skan MUGA
  • Wielobramkowe skanowanie akwizycji
  • Skanowanie ventriculogramu radionuklidów
  • Skanowanie zamkniętej puli serca
  • Skan RNV
Procedura: Biospecimen Collection

Undergo collection of blood samples

Inne nazwy:
  • Pobieranie próbek biologicznych
  • Zebrano próbki biologiczne
  • Kolekcja próbek
Procedura: Computed Tomography

Undergo CT scan

Inne nazwy:
  • Tomografia komputerowa
  • KOT
  • Skanowanie CAT
  • Tomografia komputerowa osiowa
  • Komputerowa tomografia osiowa
  • tomografia
  • Komputerowa tomografia osiowa (zabieg)
  • Tomografia komputerowa (CT).
  • Diagnostyczny skan CAT
  • Diagnostyczny typ usługi skanowania CAT
Lek: Olaparib

Given PO

Inne nazwy:
  • Lynparza
  • 2281 zł
  • AZD-2281
  • AZD2281
  • KU-0059436
  • Inhibitor PARP AZD2281
  • KU0059436
  • Olanib
  • Olaparix
  • KU 0059436
Procedura: Bone Scan

Undergo bone scan

Inne nazwy:
  • Scyntygrafia kości
Procedura: Transthoracic Echocardiography Test

Undergo TTE

Inne nazwy:
  • TTE
  • Echokardiografia przezroczysta
Aktywny 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.
Procedura: Magnetic Resonance Imaging

Undergo MRI

Inne nazwy:
  • MRI
  • Rezonans magnetyczny
  • Skanowanie rezonansu magnetycznego
  • Obrazowanie medyczne, rezonans magnetyczny / jądrowy rezonans magnetyczny
  • PAN
  • Obrazowanie MR
  • Obrazowanie NMR
  • NMRI
  • Obrazowanie magnetycznego rezonansu jądrowego
  • Obrazowanie metodą rezonansu magnetycznego (MRI)
  • sMRI
  • Rezonans magnetyczny (zabieg)
  • Strukturalny MRI
Procedura: Multigated Acquisition Scan

Undergo MUGA

Inne nazwy:
  • Skanowanie puli krwi
  • Równoważna angiografia radionuklidów
  • Bramkowane obrazowanie puli krwi
  • MUGA
  • Wentrykulografia radionuklidów
  • RNVG
  • Skanowanie SYMA
  • Zsynchronizowane skanowanie akwizycji z wieloma bramkami
  • Skan MUGA
  • Wielobramkowe skanowanie akwizycji
  • Skanowanie ventriculogramu radionuklidów
  • Skanowanie zamkniętej puli serca
  • Skan RNV
Procedura: Biospecimen Collection

Undergo collection of blood samples

Inne nazwy:
  • Pobieranie próbek biologicznych
  • Zebrano próbki biologiczne
  • Kolekcja próbek
Procedura: Computed Tomography

Undergo CT scan

Inne nazwy:
  • Tomografia komputerowa
  • KOT
  • Skanowanie CAT
  • Tomografia komputerowa osiowa
  • Komputerowa tomografia osiowa
  • tomografia
  • Komputerowa tomografia osiowa (zabieg)
  • Tomografia komputerowa (CT).
  • Diagnostyczny skan CAT
  • Diagnostyczny typ usługi skanowania CAT
Procedura: Bone Scan

Undergo bone scan

Inne nazwy:
  • Scyntygrafia kości
Procedura: Transthoracic Echocardiography Test

Undergo TTE

Inne nazwy:
  • TTE
  • Echokardiografia przezroczysta
Lek: Pazopanib

Given PO

Inne nazwy:
  • GW786034
Lek: Trabectedin

Given IV

Inne nazwy:
  • Yondelis
  • Ekteinascydyna
  • Ekteinascydyna 743
  • ET-743
  • ET 743
  • ET743

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Progression Free Survival (PFS) (Phase II)
Ramy czasowe: 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)
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Overall Response Rate
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

National Cancer Institute (NCI)

Śledczy

  • Główny śledczy: Matthew Ingham, Alliance for Clinical Trials in Oncology

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

30 marca 2023

Zakończenie podstawowe (Rzeczywisty)

13 sierpnia 2024

Ukończenie studiów (Szacowany)

30 stycznia 2027

Daty rejestracji na studia

Pierwszy przesłany

22 czerwca 2022

Pierwszy przesłany, który spełnia kryteria kontroli jakości

22 czerwca 2022

Pierwszy wysłany (Rzeczywisty)

27 czerwca 2022

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

1 października 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

30 września 2026

Ostatnia weryfikacja

1 lipca 2026

Więcej informacji

Terminy związane z tym badaniem

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • NCI-2022-05065
  • U10CA180821 (Grant/umowa NIH USA)
  • NCI-2022-05065 (Identyfikator rejestru: CTRP (Clinical Trial Reporting Program))
  • A092104 (Inny identyfikator: CTEP)
  • A092104 (Inny identyfikator: Alliance for Clinical Trials in Oncology)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

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.

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Tak

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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