A Phase II Trial of Lapatinib in Combination With Weekly Topotecan in Patients With Platinum-Refractory/Resistant Ovarian and Primary Peritoneal Carcinoma
- Determine the efficacy of lapatinib ditosylate and topotecan hydrochloride, in terms of
response, in patients with platinum-resistant or refractory ovarian epithelial or
primary peritoneal cavity carcinoma.
- Determine the overall survival time in patients treated with this regimen.
- Determine the time to progression in patients treated with this regimen.
- Assess the toxicity profile of this regimen in these patients.
- Determine the expression patterns of epidermal growth factor receptor, HER2/neu,
hypoxia-induced factor 1 alpha, CD31, breast cancer resistance protein, and
topoisomerase I by immunohistochemistry using tumor tissue from primary debulking
- Determine the feasibility of monitoring circulating tumor cells with specific
biological markers to determine or follow response in these patients.
OUTLINE: This is a multicenter study.
Patients receive oral lapatinib ditosylate once daily on days 1-28 and topotecan
hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and on day 8 of course 1 (immediately after the
topotecan infusion) and are evaluated for pharmacological studies. Tumor tissue samples
obtained at debulking surgery are examined by immunohistochemistry for epidermal growth
factor receptor, HER1, ErbB1, HER2/neu, ErbB2, hypoxia-induced factor 1 alpha, CD31,
platelet endothelial cell adhesion molecule 1, topoisomerase I, and breast cancer resistance
After the completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response Rate (Complete Response (CR) or Partial Response (PR))
Measurable disease patients: measureable disease is defined as at least one lesion whose longest diameter >= 2cm with conventional techniques or >=1cm with spiral CT Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 4 weeks apart. Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions. Non-measurable disease patients: Decrement in CA125 by > 50% Improvement in other evaluable disease
Two consecutive evaluations at least 4 weeks apart
Paul Haluska, MD, PhD
United States: Food and Drug Administration
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