AMG 706 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

A Phase II Evaluation of AMG 706 (IND # 79,697) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

RATIONALE: AMG 706 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well AMG 706 works in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

OBJECTIVES:

Primary

• To assess the activity of AMG 706, in terms of the frequency of patients with progression-free survival for at least 6 months after initiating therapy or with an objective tumor response, in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma.

Secondary

• To determine the frequency and severity of adverse events as assessed by CTCAE v3.0.
• To characterize the distribution of the progression-free and overall survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive oral AMG 706 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

DISEASE CHARACTERISTICS:

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

  • Recurrent or persistent disease

• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan

  • Must have at least one "target lesion" that can be used to assess response, as defined by RECIST criteria

    • Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented OR a biopsy is obtained to confirm persistent disease ≥ 90 days following completion of radiotherapy

• Must have received one prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for management of primary disease

  • Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment
  • One additional cytotoxic regimen for management of recurrent or persistent disease allowed
  • Patients must have a platinum-free interval of < 12 months, have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy

• Ineligible for a higher priority GOG protocol

• No pleural effusion or ascites causing grade 2 or greater dyspnea

• No history of uncontrolled CNS metastases

  • Patients with a history of CNS metastases must have their disease controlled by radiotherapy and/or surgery; have at least two imaging scans following treatment (that were no less than 30 days apart) showing no progression of any lesions and no new lesions; and be clinically stable off corticosteroids for ≥ 14 days prior to study randomization

PATIENT CHARACTERISTICS:

• GOG performance status (PS) 0-2* NOTE: *Patients who have received 2 prior regimen must have a GOG PS of 0-2 and patients who have received 2 prior regimens must have a GOG PS of 0-1

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Urine protein < 30 mg/dL by urinalyses or ≤ 1+ by urine dipstick (unless quantitative protein is < 500 mg by 24-hour urine collection)

• Bilirubin ≤ 1.5 times ULN (< 3 times ULN in patients with UGT1A1 promoter polymorphism [i.e., Gilbert syndrome] confirmed by genotyping or Invader® UGT1A1 Molecular Assay)

• AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

• Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver or bone metastases are present)

• PTT normal

• INR ≤ 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Able to swallow oral medications

• Cardiac ejection fraction normal

• No sensory and motor neuropathy > grade 2

• No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer or other specific malignancies

• No bleeding diathesis or hypercoagulopathy within the past 14 days

• No arterial or venous thrombosis within the past 12 months

• None of the following within the past 12 months:

  • Myocardial infarction
  • Cerebrovascular accident
  • Transient ischemic attack
  • Grade 2 or greater peripheral vascular disease
  • Percutaneous transluminal coronary angioplasty/stent
  • Congestive heart failure
  • Ongoing arrhythmias requiring medication
  • Unstable angina

• No average systolic blood pressure ≥ 150 mm Hg and average diastolic blood pressure ≥ 90 mm Hg

  • Patients with hypertension that is stable on a current dose of anti-hypertensives are eligible

• No history of impaired cardiac status (e.g., severe heart disease, cardiomyopathy, or congestive heart failure)

• No psychiatric, addictive, or other kind of disorder that would compromise the ability of the patient to give written informed consent

• No open wounds, ulcers, or fractures

• No active infection requiring antibiotics (with the exception of uncomplicated UTI)

• No known HIV, hepatitis B, or hepatitis C positivity

• No known hypersensitivity to AMG 706

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered form prior surgery, radiotherapy, or chemotherapy

• At least 1 week since prior hormonal therapy for the malignant tumor

  • Concurrent hormone replacement therapy allowed

• At least 3 weeks since other prior therapy directed at the malignant tumor, including biologic or immunologic agents (i.e., small molecules or murine monoclonal antibodies)

• At least 12 weeks since prior chimeric, human, or humanized monoclonal antibodies

• More than 30 days since prior investigational therapy

• More than 12 weeks since prior bevacizumab

• More than 30 days since prior VEGFR-targeted therapy, including, but not limited to, any of the following:

  • SU5416
  • SU6668
  • Sunitinib malate
  • Vandetanib
  • Vatalanib
  • AZD2171
  • AEE 788
  • Sorafenib

• More than 28 days since prior major surgery

• More than 14 days since prior minor surgery, including open breast biopsy

• More than 7 days since prior core needle biopsy or placement of a central venous access device (including portion, tunneled, or non-tunneled catheters)

• No prior cancer treatment that would contraindicate study therapy

• No prior therapy AMG 706

• No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer

  • Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years ago, and the patient remains free of recurrent or metastatic disease

• No prior non-cytotoxic chemotherapy for management of recurrent or persistent disease

• No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer

  • Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed > 3 years ago, and the patient remains free of recurrent or metastatic disease

• No concurrent coumadin-type anticoagulants, including warfarin, at doses > 1 mg/day

  • Concurrent low molecular weight heparin or low dose warfarin (i.e., ≤ 1 mg daily) for prophylaxis against central venous catheter thrombosis is allowed

• No other concurrent investigational or antineoplastic agents