Study of Oral Topotecan With Bevacizumab for Recurrent Small Cell Lung Cancer

March 22, 2012 updated by: GlaxoSmithKline

An Open-label, Multicenter, Non-comparative, Phase II Study of Oral Topotecan in Combination With Bevacizumab for Second-line Treatment in Subjects With Relapsed Small-cell Lung Cancer (SCLC)

Combination of Hycamtin (topotecan) and Avastin (bevacizumab) could allow killing of both endothelial and neoplastic cells. We postulate that addition of bevacizumab to topotecan will increase delivery of topotecan to tumor cells and may enhance activity of topotecan in patients with previously treated small cell lung cancer and improve progression free survival.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

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
    • Arkansas
      • Jonesboro, Arkansas, United States, 72401
        • GSK Investigational Site
    • Florida
      • Gainesville, Florida, United States, 32605
        • GSK Investigational Site
      • Naples, Florida, United States, 34119
        • GSK Investigational Site
    • Georgia
      • Athens, Georgia, United States, 30607
        • GSK Investigational Site
      • Macon, Georgia, United States, 31201
        • GSK Investigational Site
      • Marietta, Georgia, United States, 30060
        • GSK Investigational Site
    • Mississippi
      • Jackson, Mississippi, United States, 39202
        • GSK Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45236
        • GSK Investigational Site
    • South Carolina
      • Mt. Pleasant, South Carolina, United States, 29464
        • GSK Investigational Site
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • GSK Investigational Site
      • Memphis, Tennessee, United States, 38120
        • GSK Investigational Site
      • Memphis, Tennessee, United States, 38104
        • GSK Investigational Site
      • Nashville, Tennessee, United States, 37203
        • GSK Investigational Site
    • Texas
      • Fort Worth, Texas, United States, 76104
        • GSK Investigational Site
    • Washington
      • Seattle, Washington, United States, 98101-2795
        • GSK Investigational Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • GSK Investigational Site

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

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of SCLC.
  • First recurrence of SCLC after therapy with one prior chemotherapy regimen at initial diagnosis.
  • Relapsed SCLC of any duration (both sensitive and resistant relapse).
  • ECOG performance status of </= 2.
  • Adequate bone marrow reserve, hepatic, renal, and cardiovascular function.
  • No prior therapy with bevacizumab or any other VEGF inhibitor or topotecan

Exclusion Criteria:

  • Uncontrolled emesis, regardless of etiology.
  • Active uncontrolled infection.
  • GI conditions or drugs that could impact absorption of oral topotecan.
  • Known hypersensitivity to any component of topotecan capsule or compounds chemically related to topotecan.
  • Uncontrolled hypertension with BP>150/100.
  • Prior h/o hypertensive crisis or encephalopathy.
  • NYHA Grade II or greater congestive heart failure.
  • H/O myocardial infarction within 6 months.
  • H/O stroke or TIA within 6 months.
  • H/O thrombotic or hemorrhagic disorders.
  • Clinically significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days.
  • Anticipation of need for major surgical procedure during the study.
  • Minor surgical procedures within 7 days prior to treatment start (placement of vascular access devices is permitted).
  • H/O abdominal fistula, GI perforation, or intra-abdominal abscess within prior 6 months. Serious, non-healing wound, active ulcer, or untreated bone fracture. - H/O hemoptysis within prior 1 month.
  • Concurrent radiotherapy.
  • H/O whole lung radiation within 90 days prior to start of treatment.
  • Presence or h/o central nervous system or brain metastases.
  • H/o another malignancy other than SCLC.
  • Concurrent chemotherapy, immunotherapy, or investigational therapy for the treatment of small cell lung cancer.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Open label, Single arm
Oral topotecan + IV Bevacizumab
Drug: Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)
2.3 mg/m2 daily x 5 oral topotecan and 15 mg/kg IV bevacizumab on day 1 of every 21 days cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Progression-free Survival (PFS) at 3 Months
Time Frame: 3 months
PFS = time from initiation of drug to time of first disease progression/death due to any cause. Progression assessed using Response Evaluation Criteria (RECIST): >=20% increase in sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since treatment started, or appearance of new lesion(s). If participant did not progress or die, the time of initiation of post-treatment anti-cancer therapy or time of last contact used. PFS at 3 months calculated by taking the Kaplan-Meier (KM) estimate at 90 days from the initiation of treatment. SE = standard error.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS - Overall
Time Frame: Baseline to disease progression or death (up to 82.4 weeks)
Progression-free survival at any site was defined as the time from initiation of investigational product to the time of first documented disease progression or death due to any cause. Progression was assessed using the RECIST guidelines: >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment started, or appearance of new lesion (s). For participants who did not progress or die, the time of initiation of post-treatment anti-cancer therapy or the time of last contact was used.
Baseline to disease progression or death (up to 82.4 weeks)
Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)
Time Frame: Baseline to disease progression or death (up to 82.4 weeks)
Tumor response was determined using the RECIST guidelines.CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since treatment started; PD, >=20% increase in sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Baseline to disease progression or death (up to 82.4 weeks)
Number of Participants With a Tumor Response (CR and PR)
Time Frame: Baseline to disease progression or death (up to 82.4 weeks)
Tumor response was determined using the RECIST guidelines. CR: disappearance of all target lesions. PR: >=30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD.
Baseline to disease progression or death (up to 82.4 weeks)
Duration of Tumor Response (CR and PR)
Time Frame: Baseline to disease progression or death (up to 82.4 weeks)
Tumor response was determined using the RECIST guidelines. CR: disappearance of all target lesions. PR: >=30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. Duration of response is defined as the time from start of response (CR or PR) until progression or death due to any cause. For participants who did not progress or die, the time of initiation of post-treatment anti-cancer therapy or the time of last contact was used.
Baseline to disease progression or death (up to 82.4 weeks)
Time to Tumor Response (CR and PR)
Time Frame: Baseline to disease progression or death (up to 82.4 weeks)
Tumor response was determined using the RECIST guidelines. CR: disappearance of all target lesions. PR: >=30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. Time to response is defined as the time from initiation of investigational product to the time of first documented response (CR or PR).
Baseline to disease progression or death (up to 82.4 weeks)
Overall Survival
Time Frame: Baseline to disease progression or death (up to 82.4 weeks)
Overall survival is defined as the time from initiation of investigational product to death due to any cause. For participants who did not die, the time of last contact was used.
Baseline to disease progression or death (up to 82.4 weeks)

Collaborators and Investigators

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

Sponsor

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2008

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

June 16, 2008

First Submitted That Met QC Criteria

June 16, 2008

First Posted (Estimate)

June 17, 2008

Study Record Updates

Last Update Posted (Estimate)

March 27, 2012

Last Update Submitted That Met QC Criteria

March 22, 2012

Last Verified

March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 104864/111127

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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