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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: bevacizumab
* Drug: sunitinib
* Drug: carboplatin
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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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

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: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, SABER-L, Avastin, Sutent