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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00698516
First received: June 16, 2008
Last updated: March 22, 2012
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Recurrent Small-cell Lung Cancer (SCLC)
Lung Cancer, Small Cell
Drug: Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Percentage of Participants With Progression-free Survival (PFS) at 3 Months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • PFS - Overall [ Time Frame: Baseline to disease progression or death (up to 82.4 weeks) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With a Tumor Response (CR and PR) [ Time Frame: Baseline to disease progression or death (up to 82.4 weeks) ] [ Designated as safety issue: No ]
    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 Tumor Response (CR and PR) [ Time Frame: Baseline to disease progression or death (up to 82.4 weeks) ] [ Designated as safety issue: No ]
    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.

  • Time to Tumor Response (CR and PR) [ Time Frame: Baseline to disease progression or death (up to 82.4 weeks) ] [ Designated as safety issue: No ]
    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).

  • Overall Survival [ Time Frame: Baseline to disease progression or death (up to 82.4 weeks) ] [ Designated as safety issue: No ]
    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.


Enrollment: 50
Study Start Date: July 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)

  Eligibility

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

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.
  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: NCT00698516

Locations
United States, Arkansas
GSK Investigational Site
Jonesboro, Arkansas, United States, 72401
United States, Florida
GSK Investigational Site
Gainesville, Florida, United States, 32605
GSK Investigational Site
Naples, Florida, United States, 34119
United States, Georgia
GSK Investigational Site
Athens, Georgia, United States, 30607
GSK Investigational Site
Macon, Georgia, United States, 31201
GSK Investigational Site
Marietta, Georgia, United States, 30060
United States, Mississippi
GSK Investigational Site
Jackson, Mississippi, United States, 39202
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45236
United States, South Carolina
GSK Investigational Site
Mt. Pleasant, South Carolina, United States, 29464
United States, Tennessee
GSK Investigational Site
Chattanooga, Tennessee, United States, 37404
GSK Investigational Site
Memphis, Tennessee, United States, 38104
GSK Investigational Site
Memphis, Tennessee, United States, 38120
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Fort Worth, Texas, United States, 76104
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98101-2795
United States, Wisconsin
GSK Investigational Site
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00698516     History of Changes
Other Study ID Numbers: 104864/111127
Study First Received: June 16, 2008
Results First Received: January 13, 2011
Last Updated: March 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Bevacizumab
Small Cell Lung Cancer (SCLC)
Topotecan

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Topotecan
Bevacizumab
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014