Combination Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial 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 surgeryPatients 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.

Inclusion Criteria:

- Histologically confirmed stage III or IV ovarian epithelial or serous
primaryperitoneal carcinoma

- The following are ineligible:

- Germ cell tumors

- Sex cord-stromal tumors

- Carcinosarcomas

- Mixed Mullerian tumors or carcinosarcomas

- Metastatic carcinomas from other sites to theovary

- Low malignant potential tumors, including micropapillary serouscarcinomas

- 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

- Performance status - GOG 0-2

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- 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

- Creatinine no greater than 1.5 times ULN

- 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

- 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

- 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

- 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

- See Disease Characteristics

- No more than 12 weeks since prior surgical resection