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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Recurrent Small-cell Lung Cancer (SCLC) focused on measuring Bevacizumab, Small Cell Lung Cancer (SCLC), Topotecan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open label, Single arm

Arm Description

Oral topotecan + IV Bevacizumab

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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).

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.

Full Information

NCT ID

NCT00698516

First Posted

June 16, 2008

Last Updated

March 22, 2012

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00698516

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2011

Overall Recruitment Status

Completed

Study Start Date

July 2008 (undefined)

Primary Completion Date

May 2010 (Actual)

Study Completion Date

May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Bevacizumab, Small Cell Lung Cancer (SCLC), Topotecan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open label, Single arm

Arm Type

Experimental

Arm Description

Oral topotecan + IV Bevacizumab

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

Percentage of Participants With Progression-free Survival (PFS) at 3 Months

Description

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.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

PFS - Overall

Description

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.

Time Frame