Phase II Bevacizumab, Gemcitabine and Carboplatin in Newly Diagnosed Non-Small Cell Lung Cancer

Phase 2

Completed

Conditions: Lung Cancer
Non-small Cell Lung Cancer (NSCLC)

Interventions: Drug: Bevacizumab
Drug: Gemcitabine
Drug: Carboplatin

Registration Number: NCT00323869

Lead Sponsor: Stanford University

Brief Summary: A multi-center study of bevacizumab in combination with gemcitabine and carboplatin as treatment for newly-diagnosed advanced non-small cell lung cancer (NSCLC).

Detailed Description: This is a open-label, phase 2, single-arm, multi-center study of bevacizumab combined with gemcitabine and carboplatin. This treatment is for newly-diagnosed advanced non-small cell lung cancer (NSCLC), excluding squamous cell carcinoma. All subjects will receive 15 mg/kg bevacizumab every 3 weeks cycle, 1000 mg/m² of gemcitabine on day 1 and 8 every 3 weeks cycle and carboplatin (AUC= 5 ) every 3 weeks. Carboplasm will be administered 1 hour prior to the gemcitabine infusion, bevacizumab will be administered 1 hour following chemotherapy infusion.

Subjects will receive a maximum of 6 cycles of chemotherapy, but treatment with bevacizumab may continue as long as patients have no evidence of progressive disease and no significant treatment-related toxicities.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

Inclusion Criteria

Not provided

Exclusion Criteria

Prior systemic treatment for advanced NSCLC (one prior regimen of up to 4 cycles of neoadjuvant or adjuvant therapy for early stage disease will be allowed, if completed at least 6 months prior to study entry)
Known brain metastases
Prior treatment with bevacizumab
History of allergic reactions
Sensitivity attributed to compounds of similar chemical or biologic composition to bevacizumab
Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study
Concomitant chemotherapy, radiotherapy, or investigational agents
Evidence of bleeding diathesis
Coagulopathy
Use of anti-coagulant agents including warfarin, heparin, aspirin, NSAIDs
Pregnant
Lactating
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
Minor surgical procedures within 7 days prior to day 0
Fine needle aspirations within 7 days prior to day 0
Core biopsies within 7 days prior to day 0
Urine protein: creatinine ratio ≥ 1.0 at screening
History of abdominal fistula within 6 months prior to Day 0
Gastrointestinal perforation within 6 months prior to Day 0
Intra-abdominal abscess within 6 months prior to Day 0
Serious, non-healing wound
Ulcer
Bone fracture
Lung carcinoma of squamous cell histology
Any histology in close proximity to a major vessel
Significant cavitation as assessed by treating investigator in consultation with an attending radiologist
History of hemoptysis (bright red blood of 1/2 teaspoon or more)
Blood pressure of > 150/100 mmHg
Unstable angina
New York Heart Association (NYHA) Grade 2 or greater congestive heart failure
History of myocardial infarction within 6 months
History of stroke within 6 months
Clinically significant peripheral vascular disease
Psychiatric illness/social situations that would limit compliance with study requirements
Another active malignancy except for non-melanoma skin cancers
Inability to comply with study and/or follow-up procedures

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bevacizumab + carboplatin + gemcitabine	Gemcitabine	Bevacizumab in combination with carboplatin and gemcitabine: •Carboplatin, administered IV at area under the curve (AUC) of 5, every 3 weeks on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles. Carboplatin was administered before the gemcitabine infusion: •Gemcitabine, administered 1000 mg/m² IV on days 1 and 8 of each 3-week cycle (twice per cycle) for up to 6 cycles Bevacizumab was administered 1 hour after end of all chemotherapy infusions: •Bevacizumab was administered 15 mg/kg IV on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles in combination with chemotherapy, then continuing until evidence of progressive disease or significant treatment-related toxicity
Bevacizumab + carboplatin + gemcitabine	Carboplatin	Bevacizumab in combination with carboplatin and gemcitabine: •Carboplatin, administered IV at area under the curve (AUC) of 5, every 3 weeks on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles. Carboplatin was administered before the gemcitabine infusion: •Gemcitabine, administered 1000 mg/m² IV on days 1 and 8 of each 3-week cycle (twice per cycle) for up to 6 cycles Bevacizumab was administered 1 hour after end of all chemotherapy infusions: •Bevacizumab was administered 15 mg/kg IV on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles in combination with chemotherapy, then continuing until evidence of progressive disease or significant treatment-related toxicity
Bevacizumab + carboplatin + gemcitabine	Bevacizumab	Bevacizumab in combination with carboplatin and gemcitabine: •Carboplatin, administered IV at area under the curve (AUC) of 5, every 3 weeks on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles. Carboplatin was administered before the gemcitabine infusion: •Gemcitabine, administered 1000 mg/m² IV on days 1 and 8 of each 3-week cycle (twice per cycle) for up to 6 cycles Bevacizumab was administered 1 hour after end of all chemotherapy infusions: •Bevacizumab was administered 15 mg/kg IV on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles in combination with chemotherapy, then continuing until evidence of progressive disease or significant treatment-related toxicity

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	18 months	Median progression-free survival (PFS) was assessed as the time to disease progression; toxicity requiring treatment discontinuation; or death.

Secondary Outcome Measures

Name	Time	Method
Response Rate (CR + PR + SD)	6 weeks	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, by computed tomography (CT); bone scan; positron emission tomography (PET) scan; and/or magnetic resonance imaging (MRI) as necessary to assess diseasE Response determined as the number of subjects with any clinical response (CR + PR + SD) per RECIST criteria. * Complete Response (CR) = disappearance of all target lesions * Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions * Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, or appearance of new cancer lesions * Stable Disease (SD): No significant effect, does not meet criteria for PR or PD.
Stable Disease (SD)	6 weeks	Number of subjects with SD per RECIST criteria
Overall Survival (OS) at 24 Months	24 months	Number of subjects surviving 2 years after treatment initiation
Overall Survival (OS)	36 months	To evaluate the safety of the combination regimen.
Partial Response (PR)	6 weeks	Number of subjects with PR per RECIST criteria
Complete Response (CR)	6 weeks	Number of subjects with CR per RECIST criteria
Time-to-First Event	18 months	Median time-to-first event, with events defined as disease progression, death, or toxicity requiring drug discontinuation
Overall Survival (OS) at 12 Months	12 months	Number of subjects surviving 1 year after treatment initiation

Trial Locations

Locations (3): Santa Clara Valley Medical Center
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San Jose, California, United States
VA Palo Alto Healthcare System
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Palo Alto, California, United States
Stanford University School of Medicine
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Stanford, California, United States