Phase II trial to study the effectiveness of combining bryostatin 1 and cisplatin in treating patients who have advanced recurrent or residual ovarian epithelial, fallopian tube, or primary peritoneal cancer. 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.
PRIMARY OBJECTIVES: I. To estimate the overall response rate and the complete response rate of patients with platinum-refractory ovarian cancer who are treated with infusional Bryostatin-1 given in combination with intravenous cisplatin. II. To estimate the duration of response in these patients. III. To obtain tissue in order to evaluate the molecular determinants of apoptosis including: p53 status, WAF1/CIP1 gene expression prior to and directly after chemotherapy, bcl-2 gene expression in vivo, bcl-2/bax ratio, p21, and the extent of apoptosis determined by the TdT assay; and the molecular determinants of DNA damage and repair including: expression levels of ERCC1. OUTLINE: This is a multicenter study. Patients receive bryostatin 1 IV continuously over 72 hours immediately followed by cisplatin IV over 1 hour. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression. Patients are followed for survival. PROJECTED ACCRUAL: A total of 18-32 patients will be accrued for this study within 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
City of Hope
Duarte, California, United States
Overall survival
Time frame: Time from first day of treatment to time of death due to any cause, assessed up to 9 years
Progression-free survival
Time frame: Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 9 years
Time to progression
Time frame: Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 9 years
Response rate (CR or PR)
Exact 95% confidence intervals will be calculated.
Time frame: Up to 9 years
Time to treatment failure
Estimated using the product-limit method of Kaplan and Meier.
Time frame: Up to 9 years
Duration of response
Estimated using the product-limit method of Kaplan and Meier.
Time frame: Up to 9 years
Incidence by severity and type of toxicity based on the National Cancer Institute (NCI) Common Toxicity Criteria v2.0 and NCI Myalgia Toxicity Grading Scale
Time frame: Up to 9 years
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.
Time frame: Prior to initiation of chemotherapy
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.
Time frame: Day 5 of course 2
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