Intravenous Weekly Topotecan In Subjects With Recurrent Or Persistent Endometrial Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00267488
First received: December 20, 2005
Last updated: June 28, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to find out if Hycamtin given weekly is safe and effective for treating your endometrial cancer.


Condition Intervention Phase
Neoplasms, Endometrial
Endometrial Cancer
Drug: topotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Phase II, Multicenter Study of Intravenous Weekly Topotecan in Subjects With Recurrent or Persistent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Best Overall Response [ Time Frame: Week 0 to Week 98 when endpoints were met ] [ Designated as safety issue: No ]
    Tumor response based on GOG (Gynecological Oncology Group) modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria. A 4-point scale used specifying tumor response. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions; (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; (PD): At least a 20% increase in the sum of the LD of target lesions


Secondary Outcome Measures:
  • Time to Progression [ Time Frame: Week 0 to Week 19 when endpoints were met ] [ Designated as safety issue: No ]
    Kaplan-Meier Estimate. Time to progression is defined as time from start of treatment until the first documented sign of disease progression or death due to progressive disease. Subjects who have not progressed or died at the time of analysis will be censored at the time of initiation of alternative anti-cancer therapy or time of last contact. Percentiles represent a set of points on a scale arrived at by dividing a group into parts in order of magnitude.

  • Overall Survival [ Time Frame: Week 0 to Week 98 ] [ Designated as safety issue: No ]
    Kaplan-Meier Estimate. Overall survival is defined as time from start of treatment until death due to any cause. Subjects who are alive at the time of analysis will be censored at the time of last contact.

  • Response Duration [ Time Frame: Week 0 to week 98 ] [ Designated as safety issue: No ]
    The time from initial documented response to the first documented sign of progression or death due to progressive disease. Not calculated due to no Complete response and only 1 partial response.

  • Time to Response [ Time Frame: Week 0 to week 98 ] [ Designated as safety issue: No ]
    The time from start of treatment until the first documented response. Not calculated due to no Complete response and only 1 partial response.

  • Safety and Tolerability as Summarized Through Adverse Event Reporting [ Time Frame: Week 0 to week 98 ] [ Designated as safety issue: No ]
    AE = Adverse Event reported at a frequency of greater than or equal to 16%. SAE = Serious Adverse Events where all were reported at 0% frequency.


Enrollment: 70
Study Start Date: October 2005
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: topotecan
    Other Name: topotecan
  Eligibility

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

Inclusion Criteria:

  • A subject will be eligible for inclusion in this study only if all of the following criteria are met:
  • Subject has provided a written informed consent.
  • Subject must be female and ≥18 years of age.
  • Subjects' original endometrial carcinoma (any histologic type) must have had pathologic confirmation.
  • Subject must have recurrent or persistent endometrial cancer.
  • Subject must have at least one measurable lesion according to GOG-modified RECIST criteria.

    • Measurable disease must be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain X-ray, CT and MRI, or ≥10 mm when measured by spiral CT.
    • Measurable disease found on chest X-ray must be confirmed with CT or MRI. Either CT or MRI must be used throughout the study to further evaluate these lesions.
    • The same diagnostic method (CT, MRI, X-ray or physical exam) used to evaluate disease, must be used throughout the study to consistently evaluate lesions.
    • Palpable tumor masses that cannot be evaluated by CT or MRI scan should be evaluated by ultrasound or confirmed by biopsy.
    • Evaluable disease (measurable or non-measurable) may be in a field of prior radiation provided that at least six weeks have elapsed since receiving radiation and disease progression is clearly documented by radiographic study. It is preferential for the target lesion to be located outside an irradiated field.
    • Non-measurable disease is defined as all other lesions, including small lesions (longest diameter <20 mm with conventional techniques or <10 mm with spiral CT scan).
  • Subject has received one prior chemotherapy regimen (excluding all topoisomerase I inhibitors e.g., HYCAMTIN and irinotecan).
  • Subject is allowed to have received, but is not required to have received, one additional prior non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Non-cytotoxic (biologic or cytostatic) agents include, but are not limited to, monoclonal antibodies, cytokines, and small molecule inhibitors of signal transduction. UM2004/00031/00 CONFIDENTIAL HCT100414 20
  • Subject is at least 21 days from prior chemotherapy and at least 30 days from prior non-cytotoxic therapy and is recovered from associated toxicities.
  • Subject must not have received radiotherapy for at least seven days.
  • Subject must be at least three weeks since last major surgery (a lesser period is acceptable if deemed in the best interest of the subject). Subject must have an ECOG Performance Status of 0 or 1 (refer to
  • Appendix 4, ECOG Performance Status).
  • Subject must have, at screening, a probable life expectancy of at least three months.
  • Subject of childbearing potential must be practicing adequate contraception [e.g., oral contraceptives, diaphragm plus spermicide, or intrauterine device (IUD)] or show documented complete abstinence from intercourse for at least three months prior to study start. The same contraceptive method should be used throughout the study and continue for at least four weeks after the end of the study. A subject will be considered of childbearing potential if not surgically sterile or post-menopausal (i.e., documented absence of menses for one year prior to entry into the study).

    14. Subject must have screening laboratory criteria as follows:

    • Hemoglobin ≥ 9.0 g/dL.
    • Neutrophils ≥ 1,500/mm³ [≥1.5 x 10^9/L].
    • Platelets ≥ 100,000/mm³ [≥100.0 x 10^9/L].
    • Creatinine ≤ upper limit of normal (ULN) or creatinine clearance (Clcreat) ≥ 60mL/min.
    • Creatinine clearance should be calculated using the Cockcroft-Gault formula:

Clcreat (mL/min) = (140-age [yr] x body wt [kg] x 0.85 72 x serum creatinine [mg/dL] OR Clcreat (mL/min) = 1.05 x (140-age [yr] x body wt [kg] serum creatinine [μmol/L]

  • Serum bilirubin within normal limits.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase < 2xULN if liver metastases are absent by abdominal CT or MRI or < 5xULN if liver metastases are present.

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria are met:

  • Subject is pregnant or lactating.
  • Subject has received more than one prior chemotherapy regimen. UM2004/00031/00 CONFIDENTIAL HCT100414 21
  • Subject has concomitant or history of previous malignancies, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for five years.
  • Subject has active uncontrolled infection.
  • Subject has brain metastases as documented by CT or MRI. Note: Asymptomatic subjects do not require CT or MRI to rule out brain metastases.
  • Subject has received prior treatment with HYCAMTIN.
  • Subject has a history of an allergic reaction to compounds chemically-related to HYCAMTIN or its constituents.
  • Subject has received any investigational agent within 30 days or five half-lives (whichever is longer) prior to study entry.
  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: NCT00267488

  Show 24 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00267488     History of Changes
Other Study ID Numbers: 100414
Study First Received: December 20, 2005
Results First Received: December 5, 2008
Last Updated: June 28, 2012
Health Authority: Hungary: National Institute of Pharmacy
Canada: Canadian Institutes of Health Research
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Hycamtin
endometrial cancer
topotecan

Additional relevant MeSH terms:
Endometrial Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms
Topotecan
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014