RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is most effective in treating ovarian epithelial cancer and peritoneal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients who have stage III or stage IV ovarian cancer or primary peritoneal cancer.

OBJECTIVES:

• Compare the efficacy of paclitaxel and carboplatin with or without gemcitabine, doxorubicin HCl liposome, or topotecan, in terms of overall and progression-free survival, in patients with stage III or IV ovarian epithelial or serous primary peritoneal carcinoma.
• Determine the response rate in patients with measurable disease treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Compare the complications in patients treated with these regimens.
• Determine the dose-intensity and cumulative dose delivery for these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified into 1 of 3 strata according to extent of residual disease and plans for interval cytoreductive surgery:

• Stratum A: Optimal (microscopic or macroscopic) residual disease without plans for surgery
• Stratum B: Suboptimal residual disease without plans for surgery
• Stratum C: Suboptimal residual disease with plans for surgery Patients are randomized to 1 of 5 treatment arms.
• Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment continues every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive chemotherapy as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. Treatment continues as in arm I.
• Arm III: Patients receive chemotherapy as in arm I during courses 1-8 and doxorubicin HCl liposome IV over 1 hour on day 1 during courses 1, 3, 5, and 7. Treatment continues as in arm I.
• Arm IV: Patients receive topotecan IV over 30 minutes on days 1-3 and carboplatin IV over 30 minutes on day 3. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy.
• Arm V: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 8. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy.

Patients with initial unresectable or suboptimal residual disease (more than 1 cm) may undergo interval cytoreductive surgery between courses 4 and 5 of chemotherapy.

Patients are followed every 3 months for 2 years and then every 6 months.

PROJECTED ACCRUAL: Approximately 4,000-5,000 patients (800-1,000 per treatment arm) will be accrued for this study within 3.5-5 years.

• Ovarian Cancer
• Peritoneal Cavity Cancer

• Drug: carboplatin
• Drug: gemcitabine hydrochloride
• Drug: paclitaxel
• Drug: pegylated liposomal doxorubicin hydrochloride
• Drug: topotecan hydrochloride
• Procedure: adjuvant therapy
• Procedure: conventional surgery

• Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, Colombo N, Fowler JM, Argenta PA, De Geest K, Mutch DG, Burger RA, Swart AM, Trimble EL, Accario-Winslow C, Roth LM. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. J Clin Oncol. 2009 Mar 20;27(9):1419-25. Epub 2009 Feb 17.
• Bookman MA, Greer BE, Ozols RF. Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel vs. cisplatin and paclitaxel (GOG 158) and an update on GOG0 182-ICON5. Int J Gynecol Cancer. 2003 Nov-Dec;13(6):735-40.
• Copeland LJ, Bookman M, Trimble E; Gynecologic Oncology Group Protocol GOG 182-ICON5. Clinical trials of newer regimens for treating ovarian cancer: the rationale for Gynecologic Oncology Group Protocol GOG 182-ICON5. Gynecol Oncol. 2003 Aug;90(2 Pt 2):S1-7.
• Baysal BE, DeLoia JA, Willett-Brozick JE, Goodman MT, Brady MF, Modugno F, Lynch HT, Conley YP, Watson P, Gallion HH. Analysis of CHEK2 gene for ovarian cancer susceptibility. Gynecol Oncol. 2004 Oct;95(1):62-9.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III or IV ovarian epithelial or serous primary peritoneal carcinoma

• The following are ineligible:

  • Germ cell tumors
  • Sex cord-stromal tumors
  • Carcinosarcomas
  • Mixed Mullerian tumors or carcinosarcomas
  • Metastatic carcinomas from other sites to the ovary
  • Low malignant potential tumors, including micropapillary serous carcinomas
  • Mucinous primary peritoneal carcinoma
• Prior ovarian low malignant potential tumor (borderline carcinoma) that was surgically resected with subsequent development of invasive adenocarcinoma allowed if no prior chemotherapy
• Optimal (no greater than 1 cm) or suboptimal residual disease after initial surgery

• Prior breast cancer allowed provided the following are true:

  • Disease-free for more than 5 years
  • No prior cytotoxic chemotherapy for breast cancer

• Prior or concurrent primary endometrial cancer allowed if the following conditions are met:

  • Stage no greater than IB
  • Less than 3 mm invasion without vascular or lymphatic invasion
  • No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• GOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• No acute hepatitis

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable angina
• No myocardial infarction within the past 6 months
• No evidence of abnormal cardiac conduction (e.g., bundle branch block, heart block) unless stable for the past 6 months

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No greater than grade 1 sensory or motor neuropathy
• No active infection that requires antibiotics
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No severe or ongoing gastrointestinal bleeding that requires blood product support

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

• Prior chemotherapy for cancer involving the abdominal cavity or pelvis allowed provided the following are true:

  • More than 3 years since prior therapy
  • No evidence of recurrent disease

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to any portion of the abdominal cavity or pelvis

• Prior radiotherapy for localized breast, head and neck, or skin cancer allowed provided the following are true:

  • More than 3 years since prior therapy
  • No evidence of recurrent disease

Surgery:

• See Disease Characteristics
• No more than 12 weeks since prior surgical resection

• National Cancer Institute (NCI)
• Southwest Oncology Group
• Medical Research Council