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

Running, not enrolling · Phase 2/Phase 3

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT05432791

Run by

National Cancer Institute (NCI)

People needed

74

Starts

2023-03-30

Expected to finish

2027-01-30

Last updated by the study team

2026-08-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

Where it is running

• 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
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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