A Study of Bevacizumab in Previously Untreated Extensive-Stage Small Cell Lung Cancer (SALUTE)

Study Overview
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Brief Summary
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This is a placebo-controlled, double-blind, multicenter, randomized study for preliminary evaluation of the efficacy and safety of combining bevacizumab with cisplatin (or carboplatin) and etoposide in patients with previously untreated extensive-stage small cell lung cancer (SCLC).

Official Title
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A Placebo-Controlled, Double-Blind, Multicenter, Randomized, Phase II Study of Bevacizumab in Previously Untreated Extensive-Stage Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Chemotherapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented small cell carcinoma of the bronchus, classified as extensive-stage disease Measurable disease or lesions Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Exclusion Criteria: Life expectancy of < 12 weeks Current, recent, or planned participation in another experimental drug study Ongoing or active infection Active malignancy other than SCLC or superficial basal/squamous cell carcinoma within the previous 5 years Prior systemic therapy, radiation therapy, or surgery for SCLC Inadequate bone marrow function, renal function, or hepatic function Serum sodium of < 120 mg/dL Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy New York Heart Association Class II or greater congestive heart failure History of myocardial infarction or unstable angina within 6 months prior to study enrollment History of stroke or transient ischemic attack within 6 months prior to study enrollment Known central nervous system disease, except for brain metastases treated with whole-brain radiotherapy Significant vascular disease or recent peripheral arterial thrombosis within 6 months prior to study enrollment History of hemoptysis within 4 weeks prior to study enrollment Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of a need for a major surgical procedure during the course of the study Core biopsy or other minor surgical procedure, including placement of a vascular access device, within 7 days prior to Day 1 History of abdominal fistula or gastrointestinal perforation within 6 months prior to study enrollment Serious, non-healing wound, active ulcer, or untreated bone fracture Known hypersensitivity to any component of bevacizumab Pregnant (positive pregnancy test) or lactating

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo+Chemotherapy<br>Chemotherapy = cisplatin (or carboplatin) + etoposide | Drug: Chemotherapy<br>* Chemotherapy = cisplatin (or carboplatin) + etoposide. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.<br>Drug: Placebo<br>* Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death.<br>|
| Experimental: Bevacizumab+Chemotherapy<br>Chemotherapy = cisplatin (or carboplatin) + etoposide | Drug: Bevacizumab<br>* Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death.<br>Drug: Chemotherapy<br>* Chemotherapy = cisplatin (or carboplatin) + etoposide. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Duration of PFS, defined as the time from randomization to disease progression or on-study death, whichever occurred first. | Randomization until progression or lost to follow-up (up to 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Duration of overall survival from randomization until death or loss to follow-up | Randomization until death or lost of follow-up (up to 27 months) | 
| Percentage of Participants With an Objective Response | Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST): Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR | Randomization until progression or lost to follow-up (up to 2 years) | 
| Number of Participants With an Objective Response | Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST): Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR | Randomization until progression or lost to follow-up (up to 2 years) | 
| Duration of Objective Response | Duration of response was defined as time from the first response date to disease progression or on-study death (i.e., death occurring any time from randomization to 30 days after the final treatment with bevacizumab/placebo). Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. | Randomization until progression or lost to follow-up (up to 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avastin, SCLC, SALUTE, Lung Cancer