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

April 3, 2013 updated by: Steven Waggoner, MD

A Phase I Study of Weekly Oral Topotecan in Gynecologic Malignancies

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD)
Time Frame: Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.
Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.
Safety and tolerability
Time Frame: Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.
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
Time Frame: blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies
blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Steven Waggoner, MD

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Stephen Waggoner, MD, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

February 11, 2009

First Submitted That Met QC Criteria

February 11, 2009

First Posted (Estimate)

February 12, 2009

Study Record Updates

Last Update Posted (Estimate)

April 5, 2013

Last Update Submitted That Met QC Criteria

April 3, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE2Y08 (Other Identifier: Case Comprehensive Cancer Center)
  • P30CA043703 (U.S. NIH Grant/Contract)
  • CASE 2Y08-CC630 (Other Identifier: Cancer Center IRB)
  • NCI-2009-01290 (Registry Identifier: NCI)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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