S0200 Carboplatin With or Without Doxil in Patients With Recurrent Ovarian Cancer

A Phase III Study of Liposomal Doxorubicin Plus Carboplatin Versus Carboplatin in Platinum-Sensitive Patients With Recurrent Epithelial Ovarian and Peritoneal Carcinoma After Failure of Initial Platinum-Based Chemotherapy

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known if carboplatin is more effective with or without liposomal doxorubicin in treating recurrent ovarian epithelial or primary peritoneal cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of carboplatin with or without liposomal doxorubicin in treating patients who have recurrent ovarian epithelial or primary peritoneal cancer.

OBJECTIVES:

• Compare overall survival of patients with platinum-sensitive recurrent ovarian epithelial or primary peritoneal cancer treated with carboplatin with or without pegylated doxorubicin HCl liposome.
• Compare progression-free survival, confirmed complete response rates, and time to treatment failure in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease measurability (elevated CA 125 only vs nonmeasurable disease only with or without elevated CA 125 vs measurable disease), number of disease sites (2 or fewer vs 3 or more), and serous tumor histology (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive carboplatin IV over 15 minutes and pegylated doxorubicin HCl liposome IV over 1 hour on day 1.
• Arm II: Patients receive carboplatin IV as in arm I. Treatment in both arms repeats every 4 weeks for a total of 15 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks, every 6 months for 3 years, and then annually for 7 years.

PROJECTED ACCRUAL: A total of 900 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial carcinoma

  • Stage III or IV disease at time of initial staging laparotomy

• Primary peritoneal and mixed Mullerian tumors allowed

• No borderline ovarian tumors

• Disease progression or recurrence after a progression-free and platinum-free interval of 6-24 months after completion of first-line platinum-based chemotherapy (either single agent or combination therapy)

• Disease progression or recurrence based solely on CA 125 elevation allowed, provided that one of the following is true:

  • Prior baseline CA 125 greater than 35 U/mL and subsequent normalization of no greater than 35 U/mL must have CA 125 greater than 2 times upper limit of normal (ULN) on 2 occasions at least 1 week apart
  • Prior baseline CA 125 greater than 35 U/mL that never normalized must have CA 125 greater than 2 times the nadir value on 2 occasions at least 1 week apart
  • Prior normal baseline CA 125 (no greater than 35 U/mL) must show CA 125 greater than 2 times ULN on 2 occasions at least 1 week apart

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• Not specified

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• SGOT and/or SGPT no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN
• Bilirubin no greater than ULN

Renal

• Creatinine no greater than 1.9 mg/dL

Cardiovascular

• No New York Heart Association class II-IV cardiac disease
• No clinical evidence of congestive heart failure
• Ejection fraction greater than 50% by MUGA or 2-dimensional echocardiogram

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or incidental carcinoid cancer
• No evidence of active or uncontrolled infection
• No severe gastrointestinal symptoms (i.e., partial obstruction) and/or gastrointestinal bleeding or diarrhea
• No greater than grade 1 preexisting sensory neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 28 days since prior biologic consolidation therapy
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 28 days since prior non-platinum-containing consolidation chemotherapy
• No prior pegylated doxorubicin HCl liposome
• No prior cumulative anthracycline (e.g., doxorubicin, daunorubicin, epirubicin) dose in excess of 240 mg/m^2
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• No prior abdominopelvic irradiation
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 28 days since prior surgical debulking for disease progression or recurrence and recovered
• No concurrent surgery

Other

• No other prior treatment during the 6-24 month progression-free and platinum-free interval except up to 12 courses of consolidation therapy
• No other concurrent anticancer therapy