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

Study Overview
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Brief Summary
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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.

Official Title
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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)

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

Intervention / Treatment
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* Drug: Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bevacizumab, Small Cell Lung Cancer (SCLC), Topotecan