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

NCT00698516 | Completed Phase 2 Results

• 1 other identifier: 104864/111127
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Recurrent Small-cell Lung Cancer (SCLC); Lung Cancer, Small Cell

Keywords

Bevacizumab; Small Cell Lung Cancer (SCLC); Topotecan

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progression-free Survival (PFS) at 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 Outcomes (6)

• PFS - Overall

  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)

  Baseline to disease progression or death (up to 82.4 weeks)

• Number of Participants With a Tumor Response (CR and PR)

  Baseline to disease progression or death (up to 82.4 weeks)

• Duration of Tumor Response (CR and PR)

  Baseline to disease progression or death (up to 82.4 weeks)

• Time to Tumor Response (CR and PR)

  Baseline to disease progression or death (up to 82.4 weeks)

Study Arms (1)

Open label, Single arm

EXPERIMENTAL

Oral topotecan + IV Bevacizumab

Drug: Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)

Interventions

Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab) DRUG

2.3 mg/m2 daily x 5 oral topotecan and 15 mg/kg IV bevacizumab on day 1 of every 21 days cycle.

Open label, Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (16)

GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

GSK Investigational Site

Gainesville, Florida, 32605, United States

Location

GSK Investigational Site

Naples, Florida, 34119, United States

Location

GSK Investigational Site

Athens, Georgia, 30607, United States

Location

GSK Investigational Site

Macon, Georgia, 31201, United States

Location

GSK Investigational Site

Marietta, Georgia, 30060, United States

Location

GSK Investigational Site

Jackson, Mississippi, 39202, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45236, United States

Location

GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37404, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38104, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38120, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Seattle, Washington, 98101-2795, United States

Location

GSK Investigational Site

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Spigel DR, Waterhouse DM, Lane S, Legenne P, Bhatt K. Efficacy and safety of oral topotecan and bevacizumab combination as second-line treatment for relapsed small-cell lung cancer: an open-label multicenter single-arm phase II study. Clin Lung Cancer. 2013 Jul;14(4):356-63. doi: 10.1016/j.cllc.2012.12.003. Epub 2013 Feb 4.

  PMID: 23391616 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Topotecan; Capsules; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2008
• First Posted: June 17, 2008
• Study Start: July 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: March 27, 2012
• Results First Posted: February 3, 2011

Record last verified: 2011-03

Locations

US (16)