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

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

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).

Study Overview

• Status: Completed
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Chemotherapy; Drug: Placebo; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo+Chemotherapy; Chemotherapy = cisplatin (or carboplatin) + etoposide	Drug: Chemotherapy; 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.; Drug: Placebo; 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.
Experimental: Bevacizumab+Chemotherapy; Chemotherapy = cisplatin (or carboplatin) + etoposide	Drug: Chemotherapy; 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.; Drug: Bevacizumab; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: David Karlin, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: November 21, 2006
• First Submitted That Met QC Criteria: November 21, 2006
• First Posted (Estimate): November 23, 2006

Study Record Updates

• Last Update Posted (Estimate): April 29, 2011
• Last Update Submitted That Met QC Criteria: April 27, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Lung Cancer; Avastin; SCLC; SALUTE
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: AVF3995g