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

Phase II Trial of Bevacizumab in Combination With Gemcitabine and Carboplatin in Patients With Newly Diagnosed Non-Small Cell Lung Cancer (Excluding Squamous Cell Carcinoma)

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

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Bevacizumab; Drug: Gemcitabine; Drug: Carboplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304-1290
      • VA Palo Alto Healthcare System
    • San Jose, California, United States, 95128
      • Santa Clara Valley Medical Center
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

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 :

• Age 18 or higher
• Life expectancy of at least 3 months
• ECOG Performance status 0 to 1
• Advanced stage non-small cell lung cancer, NSCLC, Stage IIIB with malignant pleural effusion or Stage 4, excluding squamous cell histology, with measurable or evaluable disease
• No prior systemic therapy for advanced NSCLC (prior therapy for early stage disease with one regimen is acceptable if it was completed at least 6 months prior to study entry)
• Palliative radiotherapy to painful bony metastases is permitted prior to study entry if completed prior to initiation of study treatment, and there are no residual sequelae of therapy such as bone marrow suppression
• Willingness to use appropriate contraception to avoid pregnancy during the study
• Leukocytes ≥ 3,000/µL
• Absolute neutrophil count ≥ 1,500/ µL
• Platelets ≥ 100,000/ µL
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal
• Creatinine: Within normal institutional limits
• Creatinine clearance ≥ 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal
• Ability to sign informed consent

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bevacizumab + carboplatin + 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

Drug: Bevacizumab; Murine humanized anti-vascular endothelial growth factor A (VEGF-A) monoclonal antibody; Other Names: Avastin; C225; rhuMAb-VEGF; Drug: Gemcitabine; Nucleoside analog; Other Names: Gemzar; Drug: Carboplatin; Alkylating agent; Other Names: CBDCA; Paraplatin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (CR + PR + SD)	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.	6 weeks
Overall Survival (OS)	To evaluate the safety of the combination regimen.	36 months
Partial Response (PR)	Number of subjects with PR per RECIST criteria	6 weeks
Complete Response (CR)	Number of subjects with CR per RECIST criteria	6 weeks
Stable Disease (SD)	Number of subjects with SD per RECIST criteria	6 weeks
Time-to-First Event	Median time-to-first event, with events defined as disease progression, death, or toxicity requiring drug discontinuation	18 months
Overall Survival (OS) at 12 Months	Number of subjects surviving 1 year after treatment initiation	12 months
Overall Survival (OS) at 24 Months	Number of subjects surviving 2 years after treatment initiation	24 months

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Eli Lilly and Company; Genentech, Inc.
• Investigators: Principal Investigator: Heather A Wakelee, MD, Stanford University

Publications and helpful links

General Publications

• Clement-Duchene C, Krupitskaya Y, Ganjoo K, Lavori P, McMillan A, Kumar A, Zhao G, Padda S, Zhou L, Pedro-Salcedo MS, Colevas AD, Wakelee HA. A phase II first-line study of gemcitabine, carboplatin, and bevacizumab in advanced stage nonsquamous non-small cell lung cancer. J Thorac Oncol. 2010 Nov;5(11):1821-5. doi: 10.1097/JTO.0b013e3181f1d23c.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: May 8, 2006
• First Submitted That Met QC Criteria: May 8, 2006
• First Posted (Estimate): May 10, 2006

Study Record Updates

• Last Update Posted (Estimate): September 7, 2016
• Last Update Submitted That Met QC Criteria: July 30, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• 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; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Carboplatin; Bevacizumab
• Other Study ID Numbers: IRB-03730; 96655 (Other Identifier: Stanford IRB alternate number); AVF3576s; LUN0013 (Other Identifier: OnCore); NCT00323869 (Other Identifier: NCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO