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A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
erlotinib HCl
placebo
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring NSCLC, Avastin, Tarceva, Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed written informed consent Cytologically or histologically confirmed NSCLC Clinical or radiographic progression during or after first-line chemotherapy or chemoradiotherapy for NSCLC Consent to provide archival tissue for analysis is required for participation in this study Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Age ≥ 18 years Use of an acceptable means of contraception for men and women of childbearing potential International normalized ratio (INR) no greater than 1.3 and an aPTT no greater than the upper limits of normal within 28 days prior to enrollment for patients not on low-molecular-weight heparin or fondaparinux Exclusion Criteria: Squamous cell carcinoma Prior treatment with an investigational or marketed inhibitor of the Epidermal Growth Factor Receptor (EGFR) pathway or anti-angiogenesis agent Systemic chemotherapy, radiotherapy, or investigational treatment within 28 days prior to randomization Local palliative radiotherapy within 14 days prior to randomization or persistent adverse effects from radiotherapy that have not resolved to Grade 2 or less following completion of treatment Whole brain radiotherapy or stereotactic radiosurgery for brain metastases within 4 weeks of Day 0 Neurosurgery for brain metastases within 24 weeks of Day 0 Brain biopsy within 12 weeks of Day 0 Current use of dexamethasone for treatment associated with brain metastases History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation History of any of the following within 6 months prior to Day 0: serious systemic disease, uncontrolled hypertension, unstable angina, New York Heart Association (NYHA) Grade 2 or greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring medication, clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months Progressive neurologic symptoms in patients with a history of brain metastases Full-dose anticoagulation with warfarin Chronic daily use of aspirin or other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization Anticipation of need for a major surgical procedure during the course of the study Serious, non-healing wound, ulcer, or bone fracture Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption Pregnancy or breast-feeding Presence of another invasive cancer within 5 years prior to randomization Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form or their ability to comply with study requirements

Sites / Locations

  • Kaiser Permanente - Vallejo
  • University Cancer & Blood Center, LLC; Research
  • University of Kansas Medical Center
  • Anne Arundel Health System Research Instit-Annapolis Oncology Ctr

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

erlotinib HCl + bevacizumab

erlotinib HCl + placebo

Arm Description

oral erlotinib HCl 150 mg/day orally + intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle

oral erlotinib HCl 150 mg/day orally + intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle

Outcomes

Primary Outcome Measures

Overall Survival (OS) Among All Randomized Patients
Overall Survival was defined as the period from the date of randomization until the date of patient death from any cause. For patients who had not died, survival data was censored at the date of last contact.

Secondary Outcome Measures

Progression-free Survival (PFS)
PFS was defined as the time from randomization to documented disease progression, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST), or death on study treatment, whichever occurred first.
Percentage of Participants With Objective Response
Objective response was defined as a complete or partial response determined by RECIST on two consecutive occasions >= 4 weeks apart.
Duration of Objective Response
Duration of objective response was defined as the period from the date of the initial partial or complete response until the date of disease progression or death on study treatment from any cause. For patients who had not died, data was censored at the date of last contact.

Full Information

First Posted
August 12, 2005
Last Updated
December 18, 2020
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00130728
Brief Title
A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Official Title
A Phase III, Multicenter, Placebo-Controlled, Double-Blind, Randomized Clinical Trial to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva (Erlotinib) Compared With Tarceva Alone for Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) After Failure of Standard First-Line Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
June 8, 2005 (Actual)
Primary Completion Date
July 15, 2008 (Actual)
Study Completion Date
December 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

5. Study Description

Brief Summary
This is a Phase III, multicenter, placebo-controlled, double-blind, randomized study. Approximately 650 patients will be randomized in a 1:1 ratio to one of two treatment arms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
Keywords
NSCLC, Avastin, Tarceva, Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
636 (Actual)

8. Arms, Groups, and Interventions

Arm Title
erlotinib HCl + bevacizumab
Arm Type
Experimental
Arm Description
oral erlotinib HCl 150 mg/day orally + intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle
Arm Title
erlotinib HCl + placebo
Arm Type
Placebo Comparator
Arm Description
oral erlotinib HCl 150 mg/day orally + intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Intervention Description
intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle
Intervention Type
Drug
Intervention Name(s)
erlotinib HCl
Intervention Description
oral erlotinib HCl 150 mg/day orally
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle
Primary Outcome Measure Information:
Title
Overall Survival (OS) Among All Randomized Patients
Description
Overall Survival was defined as the period from the date of randomization until the date of patient death from any cause. For patients who had not died, survival data was censored at the date of last contact.
Time Frame
From the date of randomization until the date of patient death from any cause, or the date of last contact. (Up to 3.1 years)
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
PFS was defined as the time from randomization to documented disease progression, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST), or death on study treatment, whichever occurred first.
Time Frame
From randomization to documented disease progression or death on study treatment, whichever occurred first. (Up to 3.1 years)
Title
Percentage of Participants With Objective Response
Description
Objective response was defined as a complete or partial response determined by RECIST on two consecutive occasions >= 4 weeks apart.
Time Frame
The median duration of Objective response was up to 9.7 months
Title
Duration of Objective Response
Description
Duration of objective response was defined as the period from the date of the initial partial or complete response until the date of disease progression or death on study treatment from any cause. For patients who had not died, data was censored at the date of last contact.
Time Frame
Period from Objective response until disease progression or death on study treatment. (Up to 29.5 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed written informed consent Cytologically or histologically confirmed NSCLC Clinical or radiographic progression during or after first-line chemotherapy or chemoradiotherapy for NSCLC Consent to provide archival tissue for analysis is required for participation in this study Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Age ≥ 18 years Use of an acceptable means of contraception for men and women of childbearing potential International normalized ratio (INR) no greater than 1.3 and an aPTT no greater than the upper limits of normal within 28 days prior to enrollment for patients not on low-molecular-weight heparin or fondaparinux Exclusion Criteria: Squamous cell carcinoma Prior treatment with an investigational or marketed inhibitor of the Epidermal Growth Factor Receptor (EGFR) pathway or anti-angiogenesis agent Systemic chemotherapy, radiotherapy, or investigational treatment within 28 days prior to randomization Local palliative radiotherapy within 14 days prior to randomization or persistent adverse effects from radiotherapy that have not resolved to Grade 2 or less following completion of treatment Whole brain radiotherapy or stereotactic radiosurgery for brain metastases within 4 weeks of Day 0 Neurosurgery for brain metastases within 24 weeks of Day 0 Brain biopsy within 12 weeks of Day 0 Current use of dexamethasone for treatment associated with brain metastases History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation History of any of the following within 6 months prior to Day 0: serious systemic disease, uncontrolled hypertension, unstable angina, New York Heart Association (NYHA) Grade 2 or greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring medication, clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months Progressive neurologic symptoms in patients with a history of brain metastases Full-dose anticoagulation with warfarin Chronic daily use of aspirin or other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization Anticipation of need for a major surgical procedure during the course of the study Serious, non-healing wound, ulcer, or bone fracture Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption Pregnancy or breast-feeding Presence of another invasive cancer within 5 years prior to randomization Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form or their ability to comply with study requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Kaiser Permanente - Vallejo
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
University Cancer & Blood Center, LLC; Research
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Anne Arundel Health System Research Instit-Annapolis Oncology Ctr
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21621716
Citation
Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. doi: 10.1016/S0140-6736(11)60545-X.
Results Reference
derived

Learn more about this trial

A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer

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