Carboplatin in Treating Patients With Stage IC-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

OBJECTIVES:

Primary

• Compare progression-free survival of patients with stage IC-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer treated with flat-dose vs intra-patient dose-escalated carboplatin as first-line chemotherapy.

Secondary

• Compare the toxic effects of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.
• Compare overall clinical response rate and CA 125 response in patients treated with these regimens.
• Compare overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive a flat dose of carboplatin on day 1.
• Arm II: Patients receive intra-patient dose-escalated carboplatin on day 1. In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before each treatment course, and then at 2 months post-chemotherapy.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 1,300 patients (650 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cancer*

• Stage IC-IV disease
• Peritoneal carcinomatosis* (ovarian-type) must not be a mucin-secreting tumor
• Stage IC patients must have malignant cells in ascitic fluid or peritoneal washings, tumor on the surface of the ovary, or preoperative capsule rupture NOTE: * Histologic confirmation of a primary source in the ovary is not required.
• If biospy is not available, cytology showing an adenocarcinoma is allowed provided the following criteria is met:

• Patient has a pelvis (ovarian) mass AND all of the following:

• Omental cake or other metastasis is larger than 2 cm in the upper abdomen and/or regional lymph node metastasis irrespective of size OR stage IV disease
• Serum CA 125/CEA ratio > 25 or barium enema (or colonoscopy) and gastroscopy (or radiological examination of the stomach) are negative for the presence of a primary tumor and normal mammography within 6 weeks prior to study randomization
• Initial cytoreductive laparotomy or biopsy required within the past 8 weeks

• Cytoreductive surgery may or may not have been successful during staging laparotomy
• No mixed mesodermal tumors
• No borderline ovarian tumors or tumors termed "possibly malignant"
• No adenocarcinoma of unknown origin, if histologically confirmed to be a mucin-secreting tumor
• Considered unsuitable for or unwilling to receive platinum-taxane combination therapy
• No concurrent endometrial cancer

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-3

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN

Renal

• Creatinine clearance ≥ 30 mL/min

• Obstructive hydronephrosis as a cause of borderline (i.e., creatinine clearance 30-45 mL/min) renal function must be treated before study entry

Cardiovascular

• No hypertension
• No ischemic heart disease
• No myocardial infarction within the past 6 months
• No congestive heart failure

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No symptomatic peripheral neuropathy ≥ grade 2
• No uncontrolled infection
• No other severe and/or uncontrolled medical condition
• No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy
• No other concurrent cytotoxic chemotherapy until progressive disease occurs

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics