A Phase II Evaluation of Sunitinib Malate (Sutent®, SU11248, NCI-Supplied Agent , NSC # 736511, IND #74019) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus
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