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ACTIVE NOT RECRUITING

NCT05432791

PHASE2/PHASE3

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

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

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.

Official title: 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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2023-03-30

Completion Date

2027-01-30

Last Updated

2026-04-08

Healthy Volunteers

Conditions

Locally Advanced Uterine Corpus Leiomyosarcoma Metastatic Uterine Corpus Leiomyosarcoma Stage III Uterine Corpus Leiomyosarcoma AJCC v8 Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 Unresectable Uterine Corpus Leiomyosarcoma

Interventions

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

PROCEDURE

Bone Scan

Undergo bone scan

PROCEDURE

Computed Tomography

Undergo CT scan

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

DRUG

Olaparib

Given PO

DRUG

Pazopanib

Given PO

DRUG

Temozolomide

Given PO

DRUG

Trabectedin

Given IV

PROCEDURE

Transthoracic Echocardiography Test

Undergo TTE

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.

Locations (145)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Alaska Women's Cancer Care

Anchorage, Alaska, United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Epic Care-Dublin

Dublin, California, United States

Epic Care Partners in Cancer Care

Emeryville, California, United States

City of Hope at Irvine Lennar

Irvine, California, United States

Contra Costa Regional Medical Center

Martinez, California, United States

Epic Care Cyberknife Center

Walnut Creek, California, United States

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Memorial Hospital North

Colorado Springs, Colorado, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Cancer Care and Hematology-Fort Collins

Fort Collins, Colorado, United States

UCHealth Greeley Hospital

Greeley, Colorado, United States

Medical Center of the Rockies

Loveland, Colorado, United States

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, United States

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, United States

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, United States

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, United States

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, United States

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, United States

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, United States

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, United States

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, United States

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, United States

Northwestern University

Chicago, Illinois, United States

University of Illinois

Chicago, Illinois, United States

Carle at The Riverfront

Danville, Illinois, United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States

Carle Physician Group-Effingham

Effingham, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

NorthShore University HealthSystem-Glenbrook Hospital

Glenview, Illinois, United States

NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois, United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

Carle Cancer Center

Urbana, Illinois, United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Mary Greeley Medical Center

Ames, Iowa, United States

McFarland Clinic - Ames

Ames, Iowa, United States

McFarland Clinic - Boone

Boone, Iowa, United States

Heartland Oncology and Hematology LLP

Council Bluffs, Iowa, United States

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

McFarland Clinic - Jefferson

Jefferson, Iowa, United States

McFarland Clinic - Marshalltown

Marshalltown, Iowa, United States

Baptist Health Lexington

Lexington, Kentucky, United States

Our Lady of the Lake Medical Oncology

Baton Rouge, Louisiana, United States

University Medical Center New Orleans

New Orleans, Louisiana, United States

MaineHealth Maine Medical Center- Scarborough

Scarborough, Maine, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Bronson Battle Creek

Battle Creek, Michigan, United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, United States

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Beacon Kalamazoo Cancer Center

Kalamazoo, Michigan, United States

Trinity Health Muskegon Hospital

Muskegon, Michigan, United States

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, United States

Corewell Health Reed City Hospital

Reed City, Michigan, United States

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

University of Michigan Health - West

Wyoming, Michigan, United States

Mercy Hospital

Coon Rapids, Minnesota, United States

Fairview Southdale Hospital

Edina, Minnesota, United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Regions Hospital

Saint Paul, Minnesota, United States

United Hospital

Saint Paul, Minnesota, United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Siteman Cancer Center-South County

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Nebraska Cancer Specialists/Oncology Hematology West PC - MECC

Omaha, Nebraska, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Oncology Associates PC

Omaha, Nebraska, United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan Kettering Commack

Commack, New York, United States

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Northwell Health/Center for Advanced Medicine

Lake Success, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

ECU Health Medical Center

Greenville, North Carolina, United States

UH Seidman Cancer Center at UH Avon Health Center

Avon, Ohio, United States

UHHS-Chagrin Highlands Medical Center

Beachwood, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Clackamas Radiation Oncology Center

Clackamas, Oregon, United States

Legacy Mount Hood Medical Center

Gresham, Oregon, United States

Providence Newberg Medical Center

Newberg, Oregon, United States

Providence Willamette Falls Medical Center

Oregon City, Oregon, United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

Providence Portland Medical Center

Portland, Oregon, United States

Providence Saint Vincent Medical Center

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Legacy Meridian Park Hospital

Tualatin, Oregon, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Asplundh Cancer Pavilion

Willow Grove, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island, United States

Saint Joseph's/Candler - Bluffton Campus

Bluffton, South Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

University of Washington Medical Center - Montlake

Seattle, Washington, United States

Legacy Cancer Institute Medical Oncology and Day Treatment

Vancouver, Washington, United States

Legacy Salmon Creek Hospital

Vancouver, Washington, United States

West Virginia University Charleston Division

Charleston, West Virginia, United States

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, United States

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, United States

Marshfield Medical Center - Weston

Weston, Wisconsin, United States

Centro Comprensivo de Cancer de UPR

San Juan, Puerto Rico

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (145)