CP-547,632 in Treating Patients With Recurrent or Persistent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

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

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.

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