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

This study has been completed.
Sponsor:
Collaborators:
Eli Lilly and Company
Genentech, Inc.
Information provided by (Responsible Party):
Heather Wakelee, Stanford University
ClinicalTrials.gov Identifier:
NCT00323869
First received: May 8, 2006
Last updated: June 14, 2016
Last verified: June 2016
  Purpose
A multi-center study of bevacizumab in combination with gemcitabine and carboplatin as treatment for newly-diagnosed advanced non-small cell lung cancer (NSCLC).

Condition Intervention Phase
Lung Cancer
Non-small Cell Lung Cancer (NSCLC)
Drug: Bevacizumab
Drug: Gemcitabine
Drug: Carboplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Median progression-free survival (PFS) was assessed as the time to disease progression; toxicity requiring treatment discontinuation; or death.


Secondary Outcome Measures:
  • Response Rate (CR + PR + SD) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

    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.

  • Overall Survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To evaluate the safety of the combination regimen.

  • Partial Response (PR) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Number of subjects with PR per RECIST criteria

  • Complete Response (CR) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Number of subjects with CR per RECIST criteria

  • Stable Disease (SD) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Number of subjects with SD per RECIST criteria

  • Time-to-First Event [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Median time-to-first event, with events defined as disease progression, death, or toxicity requiring drug discontinuation

  • Overall Survival (OS) at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Number of subjects surviving 1 year after treatment initiation

  • Overall Survival (OS) at 24 Months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Number of subjects surviving 2 years after treatment initiation


Enrollment: 48
Study Start Date: June 2006
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Gemzar
Drug: Carboplatin
Alkylating agent
Other Names:
  • Paraplatin
  • CBDCA

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00323869

Locations
United States, California
VA Palo Alto Healthcare System
Palo Alto, California, United States, 94304-1290
Santa Clara Valley Medical Center
San Jose, California, United States, 95128
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Eli Lilly and Company
Genentech, Inc.
Investigators
Principal Investigator: Heather A Wakelee, MD Stanford University
  More Information

Publications:
Responsible Party: Heather Wakelee, Associate Professor of Medicine (Oncology), Stanford University
ClinicalTrials.gov Identifier: NCT00323869     History of Changes
Other Study ID Numbers: IRB-03730  96655  AVF3576s  LUN0013 
Study First Received: May 8, 2006
Results First Received: April 20, 2016
Last Updated: June 14, 2016
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Federal Government
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Bevacizumab
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 28, 2016