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

Inclusion Criteria

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