cp-547,632 in treating patients with recurrent or persistent ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

Conditions: Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer

Summary: 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.

objectives: primary * 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. secondary * 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.

Eligibility 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

Keywords: recurrent ovarian epithelial cancer primary peritoneal cavity cancer fallopian tube cancer