Phase II Open-Label, Multi-Center Study of CP-547, 632, an Oral Tyrosine Kinase Inhibitor of VEGFR-2, in Subjects With Recurrent or Persistent Small-Volume Epithelial Ovarian Cancer, Primary Peritoneal Serous Cancer, or Fallopian Tube Cancer
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed ovarian epithelial, primary peritoneal serous, or fallopian
tube cancer
- Recurrent or persistent disease
- Elevated CA 125, defined as ≥ 40 U/mL on 2 separate consecutive
measurements taken ≥ 1 week apart
- No definitive disease OR small-volume disease (≤ 2 cm by spiral or conventional CT
scan or clinical exam)
- Asymptomatic disease
PATIENT CHARACTERISTICS:
Age
- 26 and over (age 18 to 25 allowed provided there is closure of the epiphyses on
radiography)
Performance status
- ECOG 0-1
Life expectancy
- More than 6 months
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- No bleeding disorders
- No hemorrhage ≥ grade 2 within the past 12 months
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN
- ALT and/or AST ≤ 2.5 times ULN
- Albumin ≥ 3.2 g/dL
- PT/PTT ≤ 1.5 times ULN
- INR ≤ 1.5
Renal
- Creatinine ≤ 1.5 times ULN OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- QTc ≤ 460 msec by ECG
- No unstable angina within the past 6 months
- No decompensated congestive heart failure within the past 6 months
- No myocardial infarction within the past 6 months
- No serious cardiac arrhythmias or conduction abnormalities, including any history of
recurrent ventricular arrhythmia, within the past 6 months
- No cardiomyopathy
- No history of syncope associated with arrhythmia
- No uncontrolled hypertension within the past 3 weeks, defined as systolic blood
pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg on ≥ 2 of 3 blood
pressure readings taken ≥ 5 minutes apart
- No thrombotic cardiovascular events, including transient ischemic attacks, within the
past 12 months
Gastrointestinal
- Able to take oral medication
- No malabsorption syndromes
- No active gastrointestinal bleeding (hematemesis, hematochezia, or melena), unrelated
to cancer, within the past 3 months
- No requirement for IV alimentation
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
participation
- No active infection
- No uncontrolled diabetes
- No dementia, altered mental status, or uncontrolled psychiatric illness that would
preclude giving informed consent or study compliance
- No other serious uncontrolled medical disorder that would preclude study
participation
- No other active malignancy within the past 3 years except treated limited stage basal
cell or squamous cell skin cancer or carcinoma in situ of the breast or cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior exposure to mouse antibodies
- No prior vascular endothelial growth factor (VEGF) or VEGF-receptor targeted therapy
- No other prior antiangiogenic anticancer therapy, including thalidomide
- No concurrent prophylactic colony-stimulating factors (i.e., filgrastim [G-CSF] or
sargramostim [GM-CSF])
- No concurrent immunotherapy
Chemotherapy
- Prior chemotherapy allowed provided patient received only a first-line platinum-based
chemotherapy regimen with or without systemic consolidation chemotherapy
- At least 3 weeks since prior chemotherapy and recovered (excluding alopecia)
- No concurrent chemotherapy
Endocrine therapy
- At least 3 weeks since prior hormonal therapy for ovarian cancer and recovered
- Concurrent hormone replacement therapy allowed
- No concurrent chronic oral or IV corticosteroids
- No concurrent hormonal therapy, including tamoxifen
Radiotherapy
- No concurrent radiotherapy
Surgery
- More than 4 weeks since prior major surgical procedure
- No prior gastric resection
Other
- More than 3 weeks since prior investigational therapy
- More than 4 weeks since prior major medical interference with the peritoneum or
pleura
- More than 3 months since prior treatment for active ulcer disease
- No prior consolidation intraperitoneal therapy using cytotoxic agents for ovarian
cancer
- No concurrent antiarrhythmics
- Beta blockers or calcium channel blockers used for other indications allowed
- No concurrent grapefruit juice
- No concurrent therapeutic anticoagulant therapy or chronic daily aspirin > 325 mg/day
- Concurrent low-dose anticoagulants for maintenance of central venous access
allowed
- No other concurrent experimental or anticancer therapy for the primary disease