• Toxicity [ Designated as safety issue: Yes ]
• Quality of life [ Designated as safety issue: No ]
• Clinical overall response rate and CA125 response [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]

• Toxicity
• Quality of life
• Clinical overall response rate and CA125 response
• Overall survival

RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This randomized phase III trial is comparing different doses of carboplatin to see how well they work in treating patients with stage IC, stage II, stage III, or stage 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.

• Fallopian Tube Cancer
• Ovarian Cancer
• Peritoneal Cavity Cancer

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