Topotecan in Treating Patients With Gynecologic Cancer That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I trial is studying the side effects and best dose of topotecan in treating patients with gynecologic cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary To establish the maximum tolerated dose (MTD) of oral topotecan hydrochloride in patients with unresectable gynecologic malignancies. To determine the safety and tolerability of this drug in these patients. To obtain pharmacokinetic data to assess plasma concentrations of this drug when administered at the MTD. Secondary To explore the response in patients treated with this drug. OUTLINE: Patients receive oral topotecan hydrochloride on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients treated at the maximum tolerated dose undergo blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies.

Official Title
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A Phase I Study of Weekly Oral Topotecan in Gynecologic Malignancies

Conditions
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Cervical Cancer, Endometrial Cancer, Fallopian Tube Cancer, Ovarian Cancer, Sarcoma, Vaginal Cancer, Vulvar Cancer

Intervention / Treatment
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* Drug: topotecan hydrochloride
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically* or cytologically confirmed unresectable gynecologic malignancy for which standard curative or palliative care is not available All tumor types allowed NOTE: *Histologic confirmation of recurrence is not required Measurable or nonmeasurable disease If CT scan was used to evaluate measurable disease, lesions must be clearly defined and be ≥ 10 mm on spiral CT scan No borderline tumors or tumors with low malignant potential PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy ≥ 12 weeks ANC ≥ 1,500/μL Platelet count ≥ 100,000/μL Hemoglobin ≥ 9 g/dL Creatinine ≤ 1.5 times upper limit of normal (ULN) Creatinine clearance ≥ 60 mL/min AST/ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases are present) Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases are present) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Adequate intestinal function (i.e., no gastrostomy tube or requirement for IV hydration or nutritional support) No severe gastrointestinal bleeding or intestinal obstruction No other condition that would affect gastrointestinal absorption and motility No septicemia, severe infection, or acute hepatitis No other malignancies requiring chemotherapy or radiotherapy within the past 5 years, except skin cancer No concurrent severe medical problem unrelated to the malignancy that would significantly limit full compliance with the study, expose the patient to extreme risk, or decrease life expectancy PRIOR CONCURRENT THERAPY: At least 28 days since prior investigational drugs (including cytotoxic drugs) At least 4 weeks since prior chemotherapy, radiotherapy, biologic therapy, or surgery and recovered No more than 3 prior chemotherapy regimens No prior topotecan hydrochloride or other camptothecin analogs No prior radiotherapy to > 25% of the bone marrow No other concurrent chemotherapy, radiotherapy, biologic therapy, immunotherapy, or hormonal therapy for cancer No concurrent administration of any of the following: P-glycoprotein (ABCB1, Pgp, MDR1) inhibitors or inducers Breast cancer-resistant protein (ABCG2, BCRP, MXR) inhibitors or inducers No concurrent chronic H2 antagonists, proton pump inhibitors, or antacids for gastritis, gastroesophageal reflux disease, or gastric or duodenal ulcers Intermittent antacid therapy is allowed provided it is given ≥ 6 hours prior to and ≥ 90 minutes after study drug administration

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Topotecan<br> | Drug: topotecan hydrochloride<br>* Patients receive oral topotecan hydrochloride on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.<br>Other: pharmacological study<br>* Patients treated at the maximum tolerated dose undergo blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) |  | Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity. | 
| Safety and tolerability |  | Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity. | 
| Plasma concentration of topotecan hydrochloride when administered at the MTD |  | blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  | Treatment repeats every 28 days for up to 6 courses in the absence of disease progression. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian germ cell tumor, stage III ovarian germ cell tumor, stage IV ovarian germ cell tumor, recurrent endometrial carcinoma, stage III endometrial carcinoma, stage IV endometrial carcinoma, recurrent uterine sarcoma, stage III uterine sarcoma, stage IV uterine sarcoma, recurrent vaginal cancer, stage III vaginal cancer, stage IVA vaginal cancer, stage IVB vaginal cancer, recurrent vulvar cancer, stage III vulvar cancer, stage IV vulvar cancer, recurrent cervical cancer, stage III cervical cancer, stage IVA cervical cancer, stage IVB cervical cancer, fallopian tube cancer, ovarian sarcoma, ovarian stromal cancer