Clinical Benefit of Topoisomerase Downregulation

Study Overview
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Brief Summary
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1.1 To determine the regulation of topoisomerase I and II following alternating prolonged exposure to topotecan and etoposide (VP-16) 1.2 To determine the time to progression and the objective response rate of this treatment in patients with incurable ovarian cancer.

Detailed Description
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The rationale to study the downregulation of topoisomerase enzyme in ovarian cancer in relationship to the cell cycle distribution of the cancer cells after a prolonged continuous exposure to topo I and II poisons is to better understand the relationship between cell cycle and topo poisoning, which may lead to better clinical trial designs.

Official Title
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Clinical Benefit of Topoisomerase Downregulation: A Phase I Pilot Study

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Topotecan and VP16


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients, 18 years of age or older, with incurable ovarian advanced cancer are eligible provided that they have measurable disease by CT-scan imaging, or evaluable disease by tumor markers, following the criteria described by Rustin et al. (14). (Response to a specific treatment has occurred if after two CA-125 samples there has been a 50% decrease, confirmed by a fourth sample (50% response), or a serial decrease over three samples of greater than 75% (75% response). The final sample has to be at least 28 days after the previous sample.) Patients must have a life expectancy of at least 12 weeks. Patients must have a Zubrod performance status of 0-2. Patients must sign an informed consent. Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of > 1,500 or cells/mm3 and platelet count >100,000/mm3 and absence of a regular red blood cell transfusion requirement. Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and SGOT or SGPT < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine < 1.5 x upper limit of normal. Exclusion Criteria: Patients with symptomatic brain metastases are excluded from this study. Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. Patients may receive no other concurrent chemotherapy or radiation therapy during this trial. Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Topotecan and VP16|Course 1A: On day 1 treatment will start with a continuous infusion of TPT at 0.4 mg/m2/day for 21 days. A pump will be used to deliver the TPT. The bag in the pump will be replaced every week for sterility precautions. Course 1B: On day 28, if ANC is >1,500 and platelets > 100,000, VP-16 will be administered orally at 50 mg/day for 14 days.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the regulation of topoisomerase I and II following alternating prolonged exposure to topotecan and etoposide (VP-16) |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the time to progression and the objective response rate of this treatment in patients with incurable ovarian cancer |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Ovarian Cancer, Ovary, Cancer