A Phase II Study of Sunitinib Malate in Recurrent or Metastatic Endometrial Carcinoma

Inclusion Criteria

Criteria:

- At least 4 weeks since prior and no other concurrent investigational treatment

- At least 7 days since prior and no concurrent CYP3A4 inhibitors

- At least 12 days since prior and no concurrent CYP3A4 inducers

- No prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171,
vatalanib, VEGF Trap)

- No concurrent coumadin-derivative anticoagulants (e.g., warfarin) Thrombosis
prophylaxis therapy (2 mg daily) allowed Low molecular weight heparin allowed
provided PT/INR is =< 1.5

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies

- No concurrent agents with proarrhythmic potential including, but not limited to, the
following

- Histologically or cytologically confirmed endometrial cancer [Adenocarcinoma (e.g.,
endometrioid, serous, or papillary serous) or carcinosarcoma (e.g., malignant mixed
mullerian tumor of the uterus), no other histologies (e.g., squamous cell carcinoma
or leiomyosarcoma)]

- Patients meeting any of the following criteria are eligible provided they have normal
LVEF on ECHO or MUGA scan:

- History of congestive heart failure with NYHA =< class I and on treatment

- Prior anthracycline exposure

- Received prior central thoracic radiation that included the heart in the
radiotherapy port

- Patients with previously treated disease must have clinical or radiographic evidence
of progressive disease

- Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm with
conventional techniques or >= 10 mm with spiral CT scan (No indicator lesions
previously treated with surgery, radiotherapy, or radiofrequency ablation)

- No known brain metastases

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 3 months

- WBC >= 3,000/mm^3

- ANC >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 100 mg/dL

- Calcium =< 12.0 mg/dL

- Bilirubin normal

- AST and ALT =< 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance >= 60 mL/min

- Serum lipase or serum amylase =< 1.5 times upper limit of normal

- Magnesium >= 0.5 mmol/L

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- QTc < 500 msec

- No significant ECG abnormalities

- No serious or non-healing wound, ulcer, or bone fracture

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No pulmonary embolism within the past 12 months

- No NYHA class III or IV heart failure

- No pre-existing adrenal insufficiency (primary or secondary)

- No condition that impairs the ability to swallow and retain sunitinib malate tablets
(e.g., gastrointestinal tract disease resulting in an inability to take oral
medication; requirement for IV alimentation; prior surgical procedures affecting
absorption; or active peptic ulcer disease)

- No history of allergic reactions to compounds of similar chemical or biological
composition to sunitinib malate

- No pre-existing thyroid abnormality unable to maintain normal range thyroid function
with medication

- No concurrent uncontrolled illness including, but not limited to, ongoing or active
infection, psychiatric illness, or social situation that would preclude study
compliance

- No uncontrolled hypertension (i.e., systolic blood pressure [BP] >= 140 mm Hg or
diastolic BP >= 90 mm Hg)

- More than 4 weeks since prior chemotherapy (6 weeks for carmustine, nitrosoureas or
mitomycin C) and recovered

- No more than 6 prior courses of anthracycline chemotherapy (or < 450 mg/m^2 of
doxorubicin hydrochloride)

- No more than 1 prior cytotoxic chemotherapy regimen for recurrent, locally advanced,
or metastatic disease

- More than 4 weeks since prior radiotherapy and recovered

- At least 4 weeks since prior major surgery

- TSH, T3, or T4 normal

- No cerebrovascular accident or transient ischemic attack within the past 12 months

- No myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic
congestive heart failure, or coronary/peripheral artery bypass graft or stenting
within the past 12 months

- Histologically or cytologically confirmed endometrial cancer

- Adenocarcinoma (e.g., endometrioid, serous, or papillary serous) or carcinosarcoma
(e.g., malignant mixed müllerian tumor of the uterus)

- No other histologies (e.g., squamous cell carcinoma or leiomyosarcoma)

- Patients with previously treated disease must have clinical or radiographic evidence
of progressive disease

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm with
conventional techniques or ≥ 10 mm with spiral CT scan

- No indicator lesions previously treated with surgery, radiotherapy, or radiofrequency
ablation

- No known brain metastases

- Patients meeting any of the following criteria are eligible provided they have normal
LVEF on ECHO or MUGA scan:

- History of congestive heart failure with NYHA ≤ class I and on treatment

- Prior anthracycline exposure

- Received prior central thoracic radiation that included the heart in the radiotherapy
port

- At least 4 weeks since prior and no other concurrent investigational treatment

- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including the
following:

- Azole antifungals (ketoconazole, itraconazole)

- Clarithromycin

- Erythromycin

- Diltiazem

- Verapamil

- HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir,
nelfinavir)

- Delavirdine

- At least 12 days since prior and no concurrent CYP3A4 inducers, including the
following:

- Rifampin

- Rifabutin

- Carbamazepine

- Phenobarbital

- Phenytoin

- Hypericum perforatum (St. John's wort)

- Efavirenz

- Tipranavir

- No prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib,
AZD2171, vatalanib, VEGF Trap)

- No concurrent coumadin-derivative anticoagulants (e.g., warfarin)

- Thrombosis prophylaxis therapy (2 mg daily) allowed

- Low molecular weight heparin allowed provided PT/INR is ≤ 1.5

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies

- No concurrent agents with proarrhythmic potential including, but not limited to, the
following:

- Terfenadine

- Quinidine

- Procainamide

- Disopyramide

- Sotalol

- Probucol

- Bepridil

- Haloperidol

- Risperidone

- Indapamide

- Flecainide