RATIONALE: CP-547,632 may stop the growth of tumor cells by blocking the enzymes necessary
for their growth and by stopping blood flow to the tumor.
PURPOSE: This phase II trial is studying how well CP-547,632 works in treating patients with
recurrent or persistent ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
- Determine the efficacy of CP-547,632, in terms of clinical response benefit (CA 125
response [complete response (CR) or partial response (PR)] or stable disease ≥ 16
weeks), in patients with recurrent or persistent small-volume ovarian epithelial,
primary peritoneal serous, or fallopian tube cancer.
- Determine progression-free survival of patients treated with this drug.
- Determine CA 125 response (CR or PR) rate in patients treated with this drug.
- Determine duration of CA 125 response in patients treated with this drug.
- Determine the safety of this drug in these patients.
- Correlate the steady state plasma concentration of this drug with efficacy and toxicity
in these patients.
- Correlate clinical outcome with an angiogenic profile derived from measurement of serum
vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8
in patients treated with this drug.
- Determine changes in the Hospital Anxiety and Depression Scale (HADS) in patients
treated with this drug.
OUTLINE: This is an open-label, multicenter study.
Patients receive oral CP-547,632 once daily on days 1-28. Treatment repeats every 28 days
for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed at 30 days and then every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 10-29 patients will be accrued for this study within 1 year.
- Histologically confirmed ovarian epithelial, primary peritoneal serous, or fallopian
- 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
- 26 and over (age 18 to 25 allowed provided there is closure of the epiphyses on
- ECOG 0-1
- More than 6 months
- 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
- 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
- Creatinine ≤ 1.5 times ULN OR
- Creatinine clearance ≥ 60 mL/min
- 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
- 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
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
- 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
- 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:
- 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
- No concurrent immunotherapy
- 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
- 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
- No concurrent radiotherapy
- More than 4 weeks since prior major surgical procedure
- No prior gastric resection
- More than 3 weeks since prior investigational therapy
- More than 4 weeks since prior major medical interference with the peritoneum or
- More than 3 months since prior treatment for active ulcer disease
- No prior consolidation intraperitoneal therapy using cytotoxic agents for ovarian
- 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
- No other concurrent experimental or anticancer therapy for the primary disease