Pazopanib Hydrochloride, Paclitaxel, and Carboplatin in Treating Patients With Refractory or Resistant Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial, fallopian tube, or peritoneal carcinoma

  • Recurrent disease

• Received at least 1 prior platinum treatment and developed platinum-refractory disease (i.e., progression within 4 weeks of platinum administration) or platinum-resistant disease (i.e., progression within 6 months after the last platinum dose)

  • There is no restriction on the number of prior lines of treatment
  • Non-platinum treatment is allowed after proven platinum-resistance or -refractory disease
• Evaluable (measurable or nonmeasurable) disease according to RECIST version 1.1 criteria
• Patients with refractory disease on weekly paclitaxel and carboplatin regimen are excluded (phase II only)
• No known gastrointestinal intraluminal metastatic lesions with risk of bleeding
• No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
• No known brain metastases or leptomeningeal disease

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100 x 10^9/L
• PT, aPTT, or INR ≤ 1.2 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times ULN*
• ALT and AST ≤ 2.5 times ULN*
• Serum creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 50 mL/min
• Urine protein creatinine ratio < 1 OR 24-hour urine protein < 1 g
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during study therapy
• No other prior primary or recurrent malignancies treated within the past 2 years except for completely resected non-melanomatous skin carcinoma or successfully treated carcinoma in situ of the skin or uterine cervix
• No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs similar or related to paclitaxel, carboplatin, and pazopanib hydrochloride
• Able to receive infusions of paclitaxel and carboplatin
• Able to swallow pazopanib hydrochloride tablets
• No unstable or serious condition (e.g., uncontrolled infection requiring systemic therapy)

• No history of any of the following cardiovascular conditions within the past 6 months:

  • Myocardial infarction
  • Unstable angina
  • Symptomatic peripheral vascular disease
  • NYHA class III-IV congestive heart failure
• LVEF > 50% as assessed by ultrasound or MUGA scan, if clinically indicated

• No inadequately controlled hypertension (SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg)

  • Initiation or adjustment of blood pressure medication is permitted prior to the study entry
• No prolonged corrected QT interval (QTc) defined as > 480 msecs using Bazett formula

• No history of cerebrovascular accident within the past 6 months, including any of the following:

  • Transient ischemic attack
  • Pulmonary embolism

  • Untreated deep venous thrombosis (DVT)

    • Patients with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
• No evidence of active bleeding or bleeding diathesis

• No clinically significant gastrointestinal (GI) tract abnormalities that may increase the risk for GI bleeding including, but not limited to, any of the following:

  • Active peptic ulcer disease
  • Inflammatory bowel disease (e.g., ulcerative colitis or Crohn disease)
  • History of bowel obstruction (excluding postoperatively [i.e., within 4 weeks post surgery])
  • Other GI conditions with increased risk of perforation

• No clinically significant GI abnormalities that may affect absorption of investigational product including, but not limited to, any of the following:

  • Malabsorption syndrome
  • Major resection of stomach or small bowel
• No hemoptysis in excess of 2.5 mL (one-half teaspoon) within 8 weeks prior to first dose of study drug
• No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• No trauma within the past 28 days
• No prior non-healing wounds, fracture, or ulcer

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No ongoing toxicity from prior anticancer therapy > grade 1 and/or that is progressing in severity, except for alopecia and ≤ grade 2 peripheral neuropathy
• No cardiac angioplasty or stenting within the past 6 months
• No coronary artery bypass graft surgery within the past 6 months
• At least 14 days since prior radiotherapy, surgery, or tumor embolization , chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy (28 days for drugs with a longer half-life)
• At least 14 days since prior (28 days for drugs with a longer half-life) and no concurrent prohibited medications
• At least 28 days since prior major surgery (procedures such as catheter placement and diagnostic endoscopic procedures are not considered to be major)