Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
- Histologically confirmed leiomyosarcoma of uterine origin, as established by the site
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 to be eligible for the study.
- 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 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.
- 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).
- 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 be able to swallow oral medications.
- In order to complete the mandatory patient-completed measure, participants must be
able to speak and/or read English and Spanish.
- 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.
- In order to complete the mandatory patient-completed measure, participants must be
able to speak and/or read English and Spanish
- 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
Exclusion Criteria:
- 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.
- 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 at least one of the agents included on
the investigator's choice arm: trabectedin or pazopanib. If the patient has had prior
treatment with one of these agents, 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 may not 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.
- 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.
- 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.
- 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 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.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 6/9/23. Questions regarding updates should be directed to the study team contact.