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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00434226
• Collaborator: (none)
• Enrollment: 56
• Arms: 2

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: bevacizumab; Drug: sunitinib; Drug: carboplatin; Drug: paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Apr 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Best Response [From randomization until disease progression/recurrence]

   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.

Secondary Outcome Measures

1. Serious Adverse Events [60 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0

2. Incidence of Grade ≥ 3 Adverse Events [60 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0

3. Incidence of Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction [60 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0

4. Incidence of Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption [60 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Genentech, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00434226
• Other Study ID Numbers: AVF3996g
• First Posted: Feb 13, 2007
• Last Update Posted: Aug 21, 2009
• Last Verified: Jul 1, 2009

• Keywords provided by , ,: SABER-L; NSCLC; Avastin; Sutent
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Bevacizumab; Carboplatin; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Bevacizumab + Carboplatin/Paclitaxel + Sunitinib	Bevacizumab + Carboplatin/Paclitaxel
Arm/Group Description	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle, carboplatin/paclitaxel on the first day of each cycle for 4 cycles, and sunitinib 25 mg/day for 2 weeks, followed by 1 week of rest	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle and carboplatin/paclitaxel on the first day of each cycle for 4 cycles
Period Title: Overall Study
STARTED	30	26
COMPLETED	0	0
NOT COMPLETED	30	26

Baseline Characteristics

Arm/Group Title	Bevacizumab + Carboplatin/Paclitaxel + Sunitinib	Bevacizumab + Carboplatin/Paclitaxel	Total
Arm/Group Description	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle, carboplatin/paclitaxel on the first day of each cycle for 4 cycles, and sunitinib 25 mg/day for 2 weeks, followed by 1 week of rest	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle and carboplatin/paclitaxel on the first day of each cycle for 4 cycles	Total of all reporting groups
Overall Participants	30	26	56
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (9.5)	64.8 (10.7)	64.2 (10.0)
Age, Customized (participants) [Number]
<18 Years	0 0%	0 0%	0 0%
Between 18 and 64 Years	15 50%	13 50%	28 50%
>=65 Years	15 50%	13 50%	28 50%
Sex: Female, Male (Count of Participants)
Female	14 46.7%	12 46.2%	26 46.4%
Male	16 53.3%	14 53.8%	30 53.6%

Outcome Measures

1. Primary Outcome

Title	Best Response
Description	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.
Time Frame	From randomization until disease progression/recurrence

Outcome Measure Data

Analysis Population Description

Randomized patients with at least one scan available at baseline and post-baseline

Arm/Group Title	Bevacizumab + Carboplatin/Paclitaxel + Sunitinib	Bevacizumab + Carboplatin/Paclitaxel
Arm/Group Description	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle, carboplatin/paclitaxel on the first day of each cycle for 4 cycles, and sunitinib 25 mg/day for 2 weeks, followed by 1 week of rest	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle and carboplatin/paclitaxel on the first day of each cycle for 4 cycles
Measure Participants	25	19
Complete Response	0 0%	0 0%
Partial Response	12 40%	9 34.6%
Stable Disease	10 33.3%	9 34.6%
Progressive Disease	2 6.7%	1 3.8%
Unable to Evaluate	0 0%	0 0%
Missing	1 3.3%	0 0%

2. Secondary Outcome

Title	Serious Adverse Events
Description	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time Frame	60 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Carboplatin/Paclitaxel + Sunitinib	Bevacizumab + Carboplatin/Paclitaxel
Arm/Group Description	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle, carboplatin/paclitaxel on the first day of each cycle for 4 cycles, and sunitinib 25 mg/day for 2 weeks, followed by 1 week of rest	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle and carboplatin/paclitaxel on the first day of each cycle for 4 cycles
Measure Participants	29	26
Anaemia	0 0%	1 3.8%
Febrile Neutropenia	4 13.3%	1 3.8%
Neutropenia	1 3.3%	0 0%
Thrombocytopenia	1 3.3%	0 0%
Cardiac Arrest	1 3.3%	1 3.8%
Diarrhoea	1 3.3%	0 0%
Asthenia	0 0%	1 3.8%
Disease Progression	1 3.3%	1 3.8%
Fatigue	1 3.3%	0 0%
Pain	0 0%	1 3.8%
Hepatic Pain	0 0%	1 3.8%
Drug Hypersensitivity	0 0%	1 3.8%
Cellulitis	1 3.3%	0 0%
Bacterial Sepsis	0 0%	1 3.8%
Collapse of Lung	1 3.3%	0 0%
Platelet Count Decreased	1 3.3%	0 0%
Haemoglobin Decreased	0 0%	1 3.8%
Nutrophil Count Decreased	0 0%	1 3.8%
Dehydration	2 6.7%	1 3.8%
Back Pain	1 3.3%	0 0%
Lung Cancer Metastatic	0 0%	2 7.7%
Gastric Cancer	1 3.3%	0 0%
Non-Small Cell Lung Cancer	1 3.3%	0 0%
Confusional State	0 0%	1 3.8%
Renal Failure	0 0%	1 3.8%
Pleural Effusion	0 0%	2 7.7%
Pneumothorax	1 3.3%	0 0%
Chronic Obstructive Pulmonary Disease	0 0%	2 7.7%
Pulmonary Embolism	2 6.7%	0 0%
Dyspnoea	0 0%	1 3.8%
Haemoptysis	0 0%	1 3.8%
Pneumonitis	1 3.3%	0 0%
Pulmonary Haemorrhage	0 0%	1 3.8%
Nasal Septum Perforation	1 3.3%	0 0%
Aortic Aneurysm	1 3.3%	0 0%
Hypotension	0 0%	1 3.8%

3. Secondary Outcome

Title	Incidence of Grade ≥ 3 Adverse Events
Description	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time Frame	60 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Carboplatin/Paclitaxel + Sunitinib	Bevacizumab + Carboplatin/Paclitaxel
Arm/Group Description	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle, carboplatin/paclitaxel on the first day of each cycle for 4 cycles, and sunitinib 25 mg/day for 2 weeks, followed by 1 week of rest	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle and carboplatin/paclitaxel on the first day of each cycle for 4 cycles
Measure Participants	29	26
Anaemia	1 3.3%	0 0%
Febrile Nutropenia	4 13.3%	2 7.7%
Leukopenia	6 20%	3 11.5%
Neutropenia	18 60%	12 46.2%
Thrombocytopenia	7 23.3%	5 19.2%
Cardiac Arrest	1 3.3%	1 3.8%
Left Ventricular Dysfunction	1 3.3%	0 0%
Diarrhoea	1 3.3%	1 3.8%
Gastrointestinal Haemorrhage	1 3.3%	0 0%
Asthenia	0 0%	1 3.8%
Disease Progression	1 3.3%	1 3.8%
Fatigue	2 6.7%	3 11.5%
Pain	1 3.3%	2 7.7%
Hepatic Pain	0 0%	1 3.8%
Drug Hypersensitivity	0 0%	1 3.8%
Hypersensitivity	0 0%	1 3.8%
Bacterial Sepsis	0 0%	1 3.8%
Cellulitis	1 3.3%	0 0%
Infection	1 3.3%	0 0%
Pneumonia	0 0%	2 7.7%
Collapse of Lung	1 3.3%	0 0%
Aspartate Aminotransferase Increased	1 3.3%	0 0%
Blood Alkaline Phosphatase Increased	1 3.3%	0 0%
Fibrin D Dimer Increased	1 3.3%	0 0%
Haemoglobin Decreased	0 0%	1 3.8%
International Normalised Ratio Increased	1 3.3%	1 3.8%
Nutrophil Count Decreased	1 3.3%	1 3.8%
Platelet Count Decreased	4 13.3%	0 0%
White Blood Cell Count Decreased	2 6.7%	0 0%
Anorexia	1 3.3%	0 0%
Dehydration	2 6.7%	1 3.8%
Hyperglycaemia	0 0%	2 7.7%
Hypoalbuminaemia	1 3.3%	0 0%
Hypocalcaemia	0 0%	1 3.8%
Hyponatraemia	0 0%	2 7.7%
Arthralgia	0 0%	1 3.8%
Back Pain	1 3.3%	0 0%
Muscular Weakness	1 3.3%	0 0%
Musculoskeletal Pain	1 3.3%	0 0%
Gastric Cancer	1 3.3%	0 0%
Lung Cancer Metastatic	0 0%	2 7.7%
Metastases to Central Nervous System	1 3.3%	0 0%
Non-Small Cell Lung Cancer	1 3.3%	0 0%
Dizziness	1 3.3%	0 0%
Confusional State	0 0%	1 3.8%
Albuminuria	1 3.3%	0 0%
Renal Failure	0 0%	1 3.8%
Chronic Obstructive Pulmonary Disease	0 0%	1 3.8%
Dyspnoea	2 6.7%	2 7.7%
Pleural Effusion	0 0%	2 7.7%
Pneumonitis	1 3.3%	0 0%
Pulmonary Embolism	2 6.7%	1 3.8%
Pulmonary Haemorrhage	0 0%	1 3.8%
Leukocytoclastic Vasculitis	1 3.3%	0 0%
Rash	2 6.7%	0 0%
Aortic Aneurysm	1 3.3%	0 0%
Hypertension	3 10%	1 3.8%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Carboplatin/Paclitaxel + Sunitinib
Arm/Group Description	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle, carboplatin/paclitaxel on the first day of each cycle for 4 cycles, and sunitinib 25 mg/day for 2 weeks, followed by 1 week of rest
Measure Participants	29
Anaemia	1 3.3%
Febrile Nutropenia	2 6.7%
Leukopenia	4 13.3%
Neutropenia	11 36.7%
Thrombocytopenia	6 20%
Left Ventricular Dysfunction	1 3.3%
Diarrhoea	1 3.3%
Gastrointestinal Haemorrhage	1 3.3%
Nausea	1 3.3%
Stomatitis	1 3.3%
Disease Progression	1 3.3%
Fatigue	2 6.7%
Bronchitis	1 3.3%
Cellulitis	1 3.3%
Infection	1 3.3%
Collapse of Lung	1 3.3%
Aspartate Aminotransferase Increased	1 3.3%
Fibrin D Dimer Increased	1 3.3%
International Normalised Ratio Increased	1 3.3%
Neutrophil Count Decreased	1 3.3%
Platelet Count Decreased	5 16.7%
White Blood Cell Count Decreased	1 3.3%
Anorexia	1 3.3%
Dehydration	2 6.7%
Hypoalbuminaemia	1 3.3%
Back Pain	1 3.3%
Muscular Weakness	1 3.3%
Musculoskeletal Pain	1 3.3%
Gastric Cancer	1 3.3%
Metastases to Central Nervous System	1 3.3%
Non-Small Cell Lung Cancer	1 3.3%
Dizziness	1 3.3%
Albuminuria	1 3.3%
Pnemothorax	1 3.3%
Dyspnoea	2 6.7%
Pulmonary Embolism	2 6.7%
Leukocytoclastic Vasculitis	1 3.3%
Rash	1 3.3%
Aortic Aneurysm	1 3.3%
Hypertension	3 10%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Carboplatin/Paclitaxel + Sunitinib	Bevacizumab + Carboplatin/Paclitaxel
Arm/Group Description	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle, carboplatin/paclitaxel on the first day of each cycle for 4 cycles, and sunitinib 25 mg/day for 2 weeks, followed by 1 week of rest	Bevacizumab intravenously at a dose of 15mg/kg on the first day of each 21-day cycle and carboplatin/paclitaxel on the first day of each cycle for 4 cycles
Measure Participants	29	26
Anaemia	1 3.3%	0 0%
Febrile Nutropenia	1 3.3%	1 3.8%
Leukopenia	1 3.3%	1 3.8%
Neutropenia	3 10%	1 3.8%
Thrombocytopenia	3 10%	2 7.7%
Cardiac Arrest	0 0%	1 3.8%
Diarrhoea	1 3.3%	0 0%
Gastrointestinal Haemorrhage	1 3.3%	0 0%
Disease Progression	1 3.3%	2 7.7%
Fatigue	2 6.7%	1 3.8%
Drug Hypersensitivity	0 0%	1 3.8%
Hypersensitivity	0 0%	1 3.8%
Bronchitis	1 3.3%	0 0%
Infection	1 3.3%	0 0%
Collapse of Lung	1 3.3%	0 0%
Aspartate Aminotransferase Increased	1 3.3%	0 0%
International Normalised Ratio Increased	1 3.3%	0 0%
Neutrophil Count Decreased	0 0%	1 3.8%
Platelet Count Decreased	5 16.7%	0 0%
Dehydration	2 6.7%	0 0%
Back Pain	1 3.3%	0 0%
Gastric Cancer	1 3.3%	0 0%
Lung Cancer Metastatic	0 0%	1 3.8%
Metastases to Central Nervous System	1 3.3%	0 0%
Metastases to Liver	0 0%	1 3.8%
Non-Small Cell Lung Cancer	1 3.3%	0 0%
Albuminuria	1 3.3%	0 0%
Renal Failure	0 0%	1 3.8%
Haemoptysis	0 0%	1 3.8%
Pleural Effusion	0 0%	1 3.8%
Pneumothorax	1 3.3%	0 0%
Pulmonary Embolism	2 6.7%	0 0%
Rash	1 3.3%	0 0%
Aortic Aneurysm	1 3.3%	0 0%
Hypertension	2 6.7%	2 7.7%
Hypotension	0 0%	1 3.8%

Adverse Events

Limitations/Caveats

Based on the early safety results from this study, Genentech halted further recruitment and discontinued treatment. Insufficient efficacy data was available to perform additional analyses and limited the interpretation of the analyses performed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study.