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

Sponsor

Steven Waggoner, MD (Other)

Overall Status

Completed

CT.gov ID

NCT00842452

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

25.9

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer Endometrial Cancer Fallopian Tube Cancer Ovarian Cancer Sarcoma Vaginal Cancer Vulvar Cancer	Drug: topotecan hydrochloride Other: pharmacological study	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Weekly Oral Topotecan in Gynecologic Malignancies

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Topotecan	Drug: topotecan hydrochloride 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. Other: pharmacological study Patients treated at the maximum tolerated dose undergo blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies.

Arm

Intervention/Treatment

Experimental: Oral Topotecan

Drug: topotecan hydrochloride

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.

Other: pharmacological study

Patients treated at the maximum tolerated dose undergo blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies.

Outcome Measures

Primary Outcome Measures

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

Response [Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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