Sunitinib in Recurrent and Refractory Ovarian, Fallopian Tube and Peritoneal Carcinoma

This study used a two-stage design to evaluate efficacy of sunitinib based on overall response (OR) defined as complete response (CR) or partial response (PR). The null and alternative OR rate were 5% and 20%. If one or more patients enrolled in the stage one cohort (n=17 patients) achieved PR or better than accrual would proceed to stage two (n=18 patients). There was 42% probability of stopping the trial at stage one if the true OR rate was 5%. With 35 patients, this design had 85% power to detect the 15% difference in OR rates assuming 2-sided type I error rate of 0.05.

Inclusion criteria

• Histologically or cytologically confirmed epithelial ovarian, fallopian tube or peritoneal cancer
• Recurrent or refractory disease
• Measurable disease, defined by RECIST
• 0 to 3 prior cytotoxic chemotherapy or biologic regimens for metastatic disease
• Adverse events related to prior tumor-specific therapy must have resolved to less than or equal to grade 1 prior to study entry
• Ability to swallow oral medications
• 18 years of age or older
• ECOG Performance status must be 0-2
• Normal organ and marrow function as outlined in the protocol

Exclusion criteria

• Receiving systemic therapy less than 14 days prior to starting sunitinib
• Receiving any other investigational agent
• Received prior sunitinib
• Untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on screening CT or MRI scans
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Evidence of a bleeding diathesis. Major surgery or NCI CTCA 3.0 grade 3 or worse hemorrhage within 4 weeks of starting study treatment
• Ongoing cardiac dysrhythmias of NCI CTCAE version 3.0 grade > 2
• Pre-existing thyroid abnormality, with thyroid function tests that cannot be maintained in the normal range with medication
• Prolonged QTc interval on baseline EKG
• Uncontrolled hypertension
• Patients who are taking cytochrome P450 enzyme-inducing antiepileptic drugs, rifampin, theophylline, ketoconazole, or St. John's wort.
• Psychiatric illness or social situations that wold limit compliance with study requirements
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration
• Pregnant women
• Clinical or radiographical evidence of a small bowel obstruction
• Poor oral intake