Sunitinib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus
Recurrent Uterine Sarcoma, Uterine Leiomyosarcoma
About this trial
This is an interventional treatment trial for Recurrent Uterine Sarcoma
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed leiomyosarcoma of the uterus
- Recurrent or persistent disease
- Refractory to curative therapy or established treatments
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- Ascites and pleural effusions are not considered measurable disease
Must have ≥ 1 target lesion to assess response
- Tumors in a previously irradiated field are considered non-target lesions unless there is documented progression or biopsy-confirmed persistence ≥ 90 days after completion of radiotherapy
Received at least 1 but no more than 2 prior cytotoxic regimens
- Initial treatment may have included high-dose chemotherapy, consolidation, or extended therapy administered after surgery or nonsurgical assessment
- Cytotoxic regimens may have included any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
- Not a candidate for a higher priority GOG protocol
- No known brain metastases
- GOG performance status 0-2 (for patients who have received 1 prior regimen) OR GOG 0-1 (for patients who have received 2 prior regimens)
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- SGOT ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 1.5 times ULN
- QTc < 500 msec
- LVEF normal by echocardiogram
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment
- Patients with a pre-existing thyroid abnormality unable to maintain normal thyroid function with medication are not eligible
- No significant EKG abnormalities (i.e., no history of serious ventricular arrhythmia OR EKG with ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
- No sensory or motor neuropathy > grade 1
No NYHA class III-IV congestive heart failure
- NYHA class II cardiac dysfunction allowed
- History of NYHA class II heart failure that is asymptomatic on treatment allowed
- No active infection requiring antibiotics
- No other invasive malignancies within the past 5 years except for nonmelanoma skin cancer
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
- No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
- No gastrointestinal tract disease resulting in an inability to take oral medication
- No requirement for IV alimentation
- No active peptic ulcer disease
- No other condition that would impair ability to swallow and retain study drug
- No serious or nonhealing wound, ulcer, or bone fracture
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- No cerebrovascular accident or transient ischemic attack within the past year
- No myocardial infarction, cardiac arrhythmia, stable or unstable angina, or symptomatic congestive heart failure within the past year
- No pulmonary embolism within the past year
No uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infections
- Psychiatric illness or social situations that would preclude study compliance
- Recovered from prior surgery, chemotherapy, or radiotherapy
- Prior anthracycline exposure and central thoracic radiation that included the heart allowed provided patient has New York Heart Association (NYHA) class II cardiac function
- At least 1 week since prior hormonal therapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) or radiotherapy
- At least 4 weeks since prior major surgery
- At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and no recurrent or metastatic disease
- At least 3 years since prior adjuvant chemotherapy for localized cancer of the breast and no recurrent or metastatic disease
- No prior radiotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma
- No prior chemotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma
- No prior noncytotoxic chemotherapy for recurrent or persistent disease
- No prior surgical procedures affecting absorption
- No coronary or peripheral artery bypass graft or stenting within the past year
- No other prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, or vascular endothelial growth factor [VEGF] Trap)
- No other prior cancer treatment that would preclude study treatment
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
- Azole fungals (e.g., ketoconazole or itraconazole)
- Clarithromycin
- Erythromycin
- Diltiazem
- Verapamil
- HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)
- Delavirdine
At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:
- Rifampin
- Rifabutin
- Carbamazepine
- Phenobarbital
- Phenytoin
- Hypericum perforatum (St. John's wort)
- Efavirenz
- Tipranavir
No concurrent proarrhythmic potential agent, including any of the following:
- Terfenadine
- Quinidine
- Procainamide
- Disopyramide
- Sotalol
- Probucol
- Bepridil
- Haloperidol
- Risperidone
- Indapamide
- Flecainide
No concurrent therapeutic coumarin-derivative anticoagulants, such as warfarin
- Doses ≤ 2 mg daily allowed for prophylaxis of thrombosis
- Low molecular weight heparin allowed provided PT INR ≤ 1.5
- No concurrent amifostine or other protective agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
Sites / Locations
- Gynecologic Oncology Group
Arms of the Study
Arm 1
Experimental
Treatment (sunitinib malate)
Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.