Testing Olaparib and Temozolomide Versus the Usual Treatment for Uterine Leiomyosarcoma After Chemotherapy Has Stopped Working

May 12, 2026 updated by: National Cancer Institute (NCI)

A Randomized Phase 2/3 Study of Olaparib Plus Temozolomide Versus Investigator's Choice for the Treatment of Patients With Advanced Uterine Leiomyosarcoma After Progression on Prior Chemotherapy

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Olaparib
Given PO
Other Names:
  • Lynparza
  • AZD 2281
  • AZD-2281
  • AZD2281
  • KU-0059436
  • PARP Inhibitor AZD2281
  • KU0059436
  • Olanib
  • Olaparix
  • KU 0059436
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Drug: Temozolomide
Given PO
Other Names:
  • Temodar
  • SCH 52365
  • Temodal
  • Temcad
  • Methazolastone
  • RP-46161
  • Temomedac
  • TMZ
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Gliotem
  • Temizole
Procedure: Multigated Acquisition Scan
Undergo MUGA
Other Names:
  • Blood Pool Scan
  • Equilibrium Radionuclide Angiography
  • Gated Blood Pool Imaging
  • MUGA
  • Radionuclide Ventriculography
  • RNVG
  • SYMA Scanning
  • Synchronized Multigated Acquisition Scanning
  • MUGA Scan
  • Multi-Gated Acquisition Scan
  • Radionuclide Ventriculogram Scan
  • Gated Heart Pool Scan
  • RNV Scan
Procedure: Bone Scan
Undergo bone scan
Other Names:
  • Bone Scintigraphy
Procedure: Transthoracic Echocardiography Test
Undergo TTE
Other Names:
  • TTE
  • TRANSTHORACIC ECHOCARDIOGRAPHY
Active Comparator: 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.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Drug: Pazopanib
Given PO
Other Names:
  • GW786034
Drug: Trabectedin
Given IV
Other Names:
  • Yondelis
  • Ecteinascidin
  • Ecteinascidin 743
  • ET-743
  • ET 743
  • ET743
Procedure: Multigated Acquisition Scan
Undergo MUGA
Other Names:
  • Blood Pool Scan
  • Equilibrium Radionuclide Angiography
  • Gated Blood Pool Imaging
  • MUGA
  • Radionuclide Ventriculography
  • RNVG
  • SYMA Scanning
  • Synchronized Multigated Acquisition Scanning
  • MUGA Scan
  • Multi-Gated Acquisition Scan
  • Radionuclide Ventriculogram Scan
  • Gated Heart Pool Scan
  • RNV Scan
Procedure: Bone Scan
Undergo bone scan
Other Names:
  • Bone Scintigraphy
Procedure: Transthoracic Echocardiography Test
Undergo TTE
Other Names:
  • TTE
  • TRANSTHORACIC ECHOCARDIOGRAPHY

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) (Phase II)
Time Frame: 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)
Time Frame: 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with a genomic alteration in a homologous recombination (HR) pathway gene
Time Frame: Within 60 days of registration
Will collect results of next generation sequencing that is known to the treating investigator and was previously performed as part of the patient's clinical care, for all patients registered to the study. Will evaluate for genomic alterations in HR pathway genes. A genomic alteration is defined as a homozygous deletion or deleterious (loss-of-function) mutation in any of the pre-defined HR pathway genes.
Within 60 days of registration
Relationship between the presence of an alteration in HR pathway genes and clinical benefit from olaparib and temozolomide
Time Frame: Assessed up to 5 years
Will evaluate whether patients with an HR pathway alteration experience increased clinical benefit from olaparib and temozolomide as compared patients who lack such an alteration, as determined by objective response rate, progression-free survival and overall survival. Response rates will be compared using the Fisher's exact test, and time to event endpoints summarized using the Kaplan-Meier curves and the log-rank test.
Assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Matthew Ingham, Alliance for Clinical Trials in Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2023

Primary Completion (Actual)

August 13, 2024

Study Completion (Estimated)

January 30, 2027

Study Registration Dates

First Submitted

June 22, 2022

First Submitted That Met QC Criteria

June 22, 2022

First Posted (Actual)

June 27, 2022

Study Record Updates

Last Update Posted (Actual)

June 1, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2022-05065 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH Grant/Contract)
  • A092104 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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