Erlotinib Hydrochloride With or Without Bevacizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutations

NCT01532089 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: RC1126NCI-2012-0005311-006881P30CA015083
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 19

Brief Summary

This randomized phase II trial studies how well erlotinib hydrochloride (Tarceva) with or without bevacizumab (Avastin) works in treating patients with stage IV non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. Bevacizumab may also stop the growth of NSCLC by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether erlotinib hydrochloride is more effective when given alone or with bevacizumab in treating patients with NSCLC.

Conditions

EGFR Exon 19 Deletion Mutation; EGFR NP_005219.2:p.L858R; Lung Non-Squamous Non-Small Cell Carcinoma; Stage IV Lung Non-Small Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

  Time from randomization to disease progression and death of any cause, whichever comes first, assessed up to 6 years

Secondary Outcomes (4)

• Overall Survival

  Time from randomization to death of any causes, assessed up to 6 years

• Response Rate (Complete or Partial) to Each Treatment, Evaluated Using the New International Criteria Proposed by the Revised Response Evaluation Criteria in Solid Tumors Guidelines (Version 1.1)

  Up to 6 years

• Progression Free Survival of Patients With Different Mutation Types (Exon Deletion 19 Versus Exon 21 L858R)

  From the date of randomization to the date of disease progression or death of any cause, whichever comes first, assessed up to 6 years

• Number of Patients Experiencing Toxicity

  Up to 42 days after treatment discontinuation

Other Outcomes (5)

• EGFR Mutations Detected in Plasma Deoxyribonucleic Acid (DNA)

  Up to 6 years

• EGFR Mutations Detected in Tumor Deoxyribonucleic Acid (DNA)

  Up to 6 years

• Prevalence of EGFR T790M Resistance Mutations From Pretreatment > Tumor Biopsies Using More Sensitive Mutation Detection Methods

  Baseline

Study Arms (2)

Arm A (erlotinib hydrochloride)

ACTIVE COMPARATOR

Patients receive erlotinib hydrochloride PO QD on days 1-21. (erlotinib will no longer be supplied and all patients will be removed from study treatment. No further follow-up by any study participants as of September 1, 2019)

Drug: Erlotinib; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis

Arm B (erlotinib hydrochloride, bevacizumab)

EXPERIMENTAL

Patients receive erlotinib hydrochloride as in Arm A and bevacizumab IV over 30-90 minutes on day 1. (erlotinib will no longer be supplied and all patients will be removed from study treatment. No further follow-up by any study participants as of September 1, 2019)

Biological: Bevacizumab; Drug: Erlotinib; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501

Arm B (erlotinib hydrochloride, bevacizumab)

Erlotinib DRUG

Given PO

Arm A (erlotinib hydrochloride); Arm B (erlotinib hydrochloride, bevacizumab)

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Arm A (erlotinib hydrochloride); Arm B (erlotinib hydrochloride, bevacizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (erlotinib hydrochloride); Arm B (erlotinib hydrochloride, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic documentation of primary lung carcinoma, non-squamous histology with activating epidermal growth factor receptor (defined as deletion 19 or exon 21 L858R mutation); Note: EGFR mutation testing must be performed at a Clinical Laboratory Improvement Amendments (CLIA) certified lab; either institutional or through a commercial laboratory (e.g. Genzyme, Response Genetics, etc); the laboratory report from the commercial laboratories report the specific mutations detected, and the method of detecting the exon 19 and exon 21 L858R point mutations must be available
• Stage IV disease according to the 7th Edition of the American Joint Committee on Cancer staging system
• Measurable disease
• Life expectancy of \>= 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3 obtained =\< 14 days prior to randomization
• Platelet count \>= 100,000/mm\^3 obtained =\< 14 days prior to randomization
• Hemoglobin \>= 9.0 g/dL obtained =\< 14 days prior to randomization
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) obtained =\< 14 days prior to randomization
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2.5 x ULN in patients without liver or bone metastases; \< 5 x ULN in patients with liver or bone metastases obtained =\< 14 days prior to randomization
• Cockcroft-Gault calculated creatinine clearance of \>= 45 ml/min or creatinine =\< 1.5 x ULN obtained =\< 14 days prior to randomization
• Urine dipstick proteinuria \< 2+ or urine protein/creatinine (UPC) ratio =\< 1.0 obtained =\< 14 days prior to randomization
• Note: patients discovered to have \>= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate =\< 1 g of protein in 24 hours
• Negative pregnancy test done =\< 7 days prior to randomization, for women of childbearing potential only
• Provide informed written consent

You may not qualify if:

• Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component
• Prior chemotherapy or treatment for metastatic non-small cell lung cancer
• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive, per medical doctor (MD) discretion
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations, or any other medical condition that would limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Other active malignancy =\< 3 years prior to randomization; EXCEPTIONS: non melanotic skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer
• History of myocardial infarction or other evidence of arterial thrombotic disease (angina), symptomatic congestive heart failure (New York Heart Association \>= grade 2), unstable angina pectoris, or cardiac arrhythmia; Note: allowed only if patient has no evidence of active disease for at least 6 months prior to randomization
• History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) =\< 6 months prior to randomization
• History of bleeding diathesis or coagulopathy
• Inadequately controlled hypertension (systolic blood pressure of \> 150 mmHg or diastolic pressure \> 100 mmHg on anti-hypertensive medications); Note: history of hypertensive crisis or hypertensive encephalopathy not allowed

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (19)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Heartland Cancer Research NCORP

Decatur, Illinois, 62526, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Carle Cancer Center NCI Community Oncology Research Program

Urbana, Illinois, 61801, United States

Location

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, 48106, United States

Location

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New Hampshire Oncology Hematology PA-Hooksett

Hooksett, New Hampshire, 03106, United States

Location

Hematology Oncology Associates of Central New York-East Syracuse

East Syracuse, New York, 13057, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Upstate Carolina CCOP

Spartanburg, South Carolina, 29303, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Related Publications (1)

• Stinchcombe TE, Janne PA, Wang X, Bertino EM, Weiss J, Bazhenova L, Gu L, Lau C, Paweletz C, Jaslowski A, Gerstner GJ, Baggstrom MQ, Graziano S, Bearden J 3rd, Vokes EE. Effect of Erlotinib Plus Bevacizumab vs Erlotinib Alone on Progression-Free Survival in Patients With Advanced EGFR-Mutant Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Oct 1;5(10):1448-1455. doi: 10.1001/jamaoncol.2019.1847.

  PMID: 31393548 DERIVED

MeSH Terms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Erlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Thomas E. Stinchcombe, M.D.
• Organization: Duke University

thomas.stinchcombe@duke.edu

507/284-4565

Study Officials

• Thomas E Stinchcombe

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2012
• First Posted: February 14, 2012
• Study Start: March 16, 2012
• Primary Completion: February 13, 2018
• Study Completion: August 18, 2020
• Last Updated: October 6, 2020
• Results First Posted: December 26, 2019

Record last verified: 2020-07

Locations

US (19)