A Study of Sunitinib in Combination With Bevacizumab, Carboplatin, and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer (SABRE-L)

A Randomized, Controlled, Open-Label, Multicenter, Phase II Study of the Safety and Efficacy of Sunitinib in Combination With Bevacizumab, Carboplatin, and Paclitaxel in Previously Untreated Patients With Advanced Non-Small Cell Lung Cancer

This is a Phase II, randomized, controlled, open-label, multicenter trial designed to provide a preliminary assessment of the safety and efficacy of sunitinib when combined with carboplatin and paclitaxel chemotherapy and bevacizumab in patients with locally advanced, recurrent or metastatic NSCLC who have not received prior systemic therapy for NSCLC. All patients will have advanced, histologically or cytologically confirmed NSCLC (Stage IIIb with pleural effusions, Stage IV, or recurrent).

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: bevacizumab; Drug: sunitinib; Drug: carboplatin; Drug: paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 56
• 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:

• Signed Informed Consent Form
• Age ≥ 18 years
• Advanced histologically or cytologically confirmed NSCLC (Stage IIIb with malignant pleural or pericardial effusion, Stage IV, or recurrent)
• Measurable or non-measurable disease
• Patients with treated brain metastases are eligible if there is no evidence of progression or hemorrhage after treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period (brain imaging to be competed Day -7 to Day 1).
• Prior treatment for CNS disease as deemed appropriate by the treating physician
• ECOG performance status 0 or 1
• Ability and willingness to comply with study and follow-up procedures

Exclusion Criteria:

• Prior systemic chemotherapy for metastatic disease
• Active malignancy other than lung cancer
• Current, recent, or planned participation in another experimental drug study
• Prior treatment with anti-VEGF agent or agents targeting similar pathways as sunitinib
• Adjuvant chemotherapy or prior combined modality neoadjuvant therapy (chemotherapy plus radiotherapy with or without surgery) within 6 months prior to Day 1 of Cycle 1
• Life expectancy of < 12 weeks
• Current, recent, or planned participation in an experimental drug study
• Inability to take oral medication or requirement of IV alimentation or total parenteral nutrition, or prior surgical procedures affecting absorption
• Inadequate organ function
• Known evidence of disseminated intravascular coagulopathy
• Active infection or fever > 38.5°C within 3 days prior to Day 1 of Cycle 1
• Untreated abnormal thyroid function tests as defined by institutional standards (patients with controlled hypothyroidism are eligible for study participation)
• Any other medical condition(s) (including mental illness or substance abuse) deemed by the clinician to be likely to interfere with a patient's ability to provide informed consent, cooperate, or participate in the study, or to interfere with the interpretation of the results
• Intrathoracic lung carcinoma of squamous cell histology
• Known CNS disease except for treated brain metastases
• Inadequately controlled hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Class II or greater CHF
• History of myocardial infarction or unstable angina within 12 months prior to Day 1 of Cycle 1
• History of stroke or transient ischemic attack within 12 months prior to Day 1 of Cycle 1
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1 of Cycle 1
• History of hemoptysis within 1 month prior to Day 1 of Cycle 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 of Cycle 1
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 of Cycle 1
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria at screening, as demonstrated by a urine protein/creatinine ratio of ≥ 1.0 at screening
• Known hypersensitivity to any component of bevacizumab or sunitinib
• Pregnancy (positive pregnancy test) or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab + Carboplatin/Paclitaxel + Sunitinib	Drug: bevacizumab; Intravenously at a dose of 15mg/kg on the first day of each 21-day cycle; Drug: sunitinib; 25 mg/day for 2 weeks, followed by 1 week of rest; Drug: carboplatin; On the first day of each cycle for 4 cycles; Drug: paclitaxel; On the first day of each cycle for 4 cycles
Placebo Comparator: Bevacizumab + Carboplatin/Paclitaxel	Drug: bevacizumab; Intravenously at a dose of 15mg/kg on the first day of each 21-day cycle; Drug: carboplatin; On the first day of each cycle for 4 cycles; Drug: paclitaxel; On the first day of each cycle for 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response	The best overall response is the best response, per RECIST criteria, recorded from randomization until disease progression/recurrence (includes both confirmed and unconfirmed responses). Although the original primary outcome was progression-free survival, there was insufficient data available to report on that outcome.	From randomization until disease progression/recurrence

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0	60 days following the last administration of study treatment
Incidence of Grade ≥ 3 Adverse Events	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0	60 days following the last administration of study treatment
Incidence of Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0	60 days following the last administration of study treatment
Incidence of Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0	60 days following the last administration of study treatment

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Julie Hambleton, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: February 11, 2007
• First Submitted That Met QC Criteria: February 11, 2007
• First Posted (Estimate): February 13, 2007

Study Record Updates

• Last Update Posted (Estimate): August 21, 2009
• Last Update Submitted That Met QC Criteria: July 9, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: NSCLC; Avastin; Sutent; SABER-L
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Sunitinib; Bevacizumab
• Other Study ID Numbers: AVF3996g