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

Lung Cancer, Small Cell Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00698516
• Other study ID #: 104864/111127
• Status: Completed
• Phase: Phase 2
• First received: June 16, 2008
• Last updated: March 22, 2012
• Start date: July 2008
• Est. completion date: May 2010

Study information

• Verified date: March 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Cancer, Small Cell
• Lung Neoplasms
• Recurrent Small-cell Lung Cancer (SCLC)
• Small Cell Lung Carcinoma

Intervention

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.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Athens	Georgia
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Jackson	Mississippi
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Macon	Georgia
United States	GSK Investigational Site	Madison	Wisconsin
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Mt. Pleasant	South Carolina
United States	GSK Investigational Site	Naples	Florida
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	PFS - Overall	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)	No
Secondary	Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)	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)	No
Secondary	Number of Participants With a Tumor Response (CR and PR)	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)	No
Secondary	Duration of Tumor Response (CR and PR)	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)	No
Secondary	Time to Tumor Response (CR and PR)	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)	No
Secondary	Overall Survival	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)	No