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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Steven Waggoner, MD, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00842452
First received: February 11, 2009
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Cervical Cancer
Endometrial Cancer
Fallopian Tube Cancer
Ovarian Cancer
Sarcoma
Vaginal Cancer
Vulvar Cancer
Drug: topotecan hydrochloride
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Weekly Oral Topotecan in Gynecologic Malignancies

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity. ] [ Designated as safety issue: Yes ]
  • Safety and tolerability [ Time Frame: Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity. ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response [ Time Frame: Treatment repeats every 28 days for up to 6 courses in the absence of disease progression. ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: February 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00842452

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Steven Waggoner, MD
Investigators
Principal Investigator: Stephen Waggoner, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Steven Waggoner, MD, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00842452     History of Changes
Other Study ID Numbers: CASE2Y08, P30CA043703, CASE2Y08, CASE 2Y08-CC630, NCI-2009-01290
Study First Received: February 11, 2009
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Sarcoma
Ovarian Neoplasms
Uterine Cervical Neoplasms
Fallopian Tube Neoplasms
Vulvar Neoplasms
Vaginal Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Fallopian Tube Diseases
Vulvar Diseases
Vaginal Diseases
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014