A Randomized Phase II Trial of Paclitaxel and Carboplatin vs. Bleomycin, Etoposide, and Cisplatin for Newly Diagnosed Advanced Stage and Recurrent Chemonaive Sex Cord-Stromal Tumors of the Ovary
A Randomized Phase II Trial of Paclitaxel and Carboplatin vs. Bleomycin, Etoposide, and Cisplatin for Newly Diagnosed Advanced Stage and Recurrent Chemonaive Sex Cord-Stromal Tumors of the Ovary
This randomized phase II trial studies paclitaxel and carboplatin to see how well they work compared with bleomycin sulfate, etoposide phosphate, and cisplatin in treating patients with sex cord-ovarian stromal tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or has returned (recurrent). Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective in treating sex cord-ovarian stromal tumors.
PRIMARY OBJECTIVES:
I. To assess the activity of paclitaxel and carboplatin with respect to progression free survival (using bleomycin, etoposide, and cisplatin [BEP] as a reference) for newly diagnosed advanced or recurrent chemonaive ovarian sex cord-stromal tumors.
SECONDARY OBJECTIVES:
I. To estimate the toxicity of paclitaxel and carboplatin, and bleomycin, etoposide, and cisplatin in this patient population.
II. To estimate overall survival for paclitaxel and carboplatin relative to that of BEP.
III. To evaluate response rate in the subset of patients with measurable disease.
TERTIARY OBJECTIVES:
I. To collect fixed and/or frozen tumor tissue for future translational research studies.
II. To explore the utility of inhibin A and inhibin B as prognostic and predictive biomarkers for ovarian sex cord-stromal tumors and to examine changes in these markers with treatment.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive bleomycin sulfate IV on day 1 and etoposide phosphate* IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients who have received prior radiotherapy receive etoposide phosphate on days 1-4.
After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Inclusion Criteria:
Patients with histologically confirmed ovarian stromal tumor [granulosa cell tumor, ganulosa cell-theca cell tumor, Sertoli-Leydig cell tumor (androblastoma), steroid (lipid) cell tumor, gynandroblastoma, unclassified sex cord-stromal tumor, sex cord tumor with annular tubules]
Patients must have newly diagnosed, stage IIA - IV disease and must be entered within eight weeks from surgery; they may have either measurable residual disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, or they may have no measurable residual disease; OR, they must have biopsy-proven recurrent disease of any stage and have never received cytotoxic chemotherapy
Patients must have a Gynecologic Oncology Group (GOG) performance grade of 0, 1, or 2
Patients of childbearing potential must have a negative serum pregnancy test and must agree to practice an effective means of birth control
Patients in the measureable disease cohort must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to Common Terminology Criteria for Adverse Events (CTCAE) grade 1
Platelet greater than or equal to 100,000/mcl
Creatinine no greater than the institutional upper limits of normal
Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (CTCAE grade 1)
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3.0 x ULN (CTCAE grade 1)
Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE grade 1)
Neuropathy (sensory and motor) less than or equal to CTCAE grade 1
No signs of clinically significant hearing loss
Patients must have signed an approved informed consent and authorization permitting release of personal health information
Patients must have pulmonary function sufficient to receive bleomycin, with normal lung expansion, absence of crackles on auscultation, and normal carbon monoxide diffusion (DLCO), defined as greater than 80% predicted
Patients with a history of hypersensitivity reactions to prior chemotherapy administered for previous cancer diagnoses are eligible to participate in the study, unless the hypersensitivity reaction consisted of anaphylaxis not amenable to desensitization
Recovery from effects of recent surgery, radiotherapy, or chemotherapy
Exclusion Criteria:
Burbank, California 91505, United States
Sylmar, California 91342, United States
Highland Park, Illinois 60035, United States
Pekin, Illinois 61554, United States
Baltimore, Maryland 21237, United States
North Kansas City, Missouri 64116, United States
Sturgeon Bay, Wisconsin 54235-1495, United States