Erlotinib or Placebo Following Chemoradiotherapy (Chemo/RT) in Stage III Non-Small Cell Lung Cancer (NSCLC)

A National Web-Based Randomized Phase III Study of Erlotinib or Placebo Following Concurrent Docetaxel, Carboplatin, and Thoracic Radiotherapy in Patients With Inoperable Stage III Non-Small Cell Lung Cancer (D0410).

This is a national, randomized, web-based, double-blind study to determine whether erlotinib (Tarceva) compared to placebo improves progression-free survival (PFS) for patients with inoperable, stage III NSCLC following concurrent docetaxel, carboplatin and thoracic radiotherapy. We hypothesize that the introduction of this orally active, well-tolerated agent following concurrent chemoradiation and prior to the emergence of drug resistance will prolong the progression-free survival by 40% (10 months → 14 months).

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung; NSCLC; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Erlotinib (tarceva); Drug: Placebo

Detailed Description

The promising activity of erlotinib as a single agent in advanced refractory NSCLC along with its oral administration and favorable adverse event profile makes this agent an excellent candidate to incorporate into combined modality therapy in the early stages of lung cancer. Based on these data, erlotinib is an attractive novel approach to maintenance therapy in unresectable stage III NSCLC following completion of concomitant chemoradiation. Although, a subset of patients with unresectable stage III NSCLC will be long-term survivors following chemotherapy and thoracic radiation therapy, the vast majority relapse within the first year following therapy and eventually die from chemotherapy refractory disease. We hypothesize that the introduction of an potent tyrosine kinase inhibitor to the epidermal growth factor receptor following effective concomitant chemoradiotherapy with docetaxel and carboplatin will prolong the progression-free survival time for these patients.

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Birmingham Hematology and Oncology Associates, LLC
    • Huntsville, Alabama, United States, 35801
      • Oncology Specialties, P.C.
  • Arkansas
    • Fort Smith, Arkansas, United States, 72913
      • Cooper Clinic
    • Hot Springs, Arkansas, United States, 71913
      • Genesis Cancer Center
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Comprehensive Cancer Center
    • Redding, California, United States, 96001
      • Northstate Cancer Speciality
    • Sacramento, California, United States, 95816
      • Mercy General Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • St. Francis Hospital Cancer Center
    • Middletown, Connecticut, United States, 06457
      • Connecticut Oncology Group
    • New Britain, Connecticut, United States, 06050
      • George Bray Cancer Center/New Britain General Hospital
    • New London, Connecticut, United States, 06320
      • Oncology and Hematology Associates, PC
    • Norwalk, Connecticut, United States, 06856
      • Whittingham Cancer Center at Norwalk Hospital
    • Stamford, Connecticut, United States, 06902
      • Hematology/Oncology PC/Carl and Dorothy Bennet Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Institute
  • Florida
    • Brooksville, Florida, United States, 34613
      • Pasco Hernando Oncology Associates
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33919
      • Lee Cancer Clinic
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Lake City, Florida, United States, 32055
      • Cancer Care of North Florida
    • New Port Richey, Florida, United States, 34652
      • Pasco/Hernando Oncology
    • Orange City, Florida, United States, 32763
      • Mid Florida Oncology
    • Orlando, Florida, United States, 32806
      • MD Anderson
    • Tamarac, Florida, United States, 33321
      • Oncology & Hematology Association of West Broward
    • West Palm Beach, Florida, United States, 33410
      • Palm Beach Cancer Institute
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Hospital Network
    • Joliet, Illinois, United States, 60435
      • Joliet Hematology Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Investigative Clinical Research of Indiana LLC
    • Kokomo, Indiana, United States, 46904
      • Howard Regional Health System
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Kentucky Cancer Clinic
    • Paducah, Kentucky, United States, 42003
      • Western Hematology Oncology
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Center for Cancer Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21218
      • Union Memorial Hospital
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital Center
    • Baltimore, Maryland, United States, 21225
      • Harbor View Cancer Center
    • Chevy Chase, Maryland, United States, 20815
      • Frederick Smith, MD
    • Olney, Maryland, United States, 20832
      • Community Hematology Oncology
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center
    • Worcester, Massachusetts, United States, 01608
      • Fallon Clinic Hematology/ Oncology
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Bay Medical Cancer Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Southeast Nebraska Hematology/Oncology
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation
  • New Hampshire
    • Keene, New Hampshire, United States, 03431
      • Dartmouth-Hitchcock-Keene
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center
  • New Jersey
    • Cherry Hill, New Jersey, United States, 00000
      • The Center for Cancer and Hematologic Disease
    • Newton, New Jersey, United States, 07860
      • Sussex County Medical Associates
  • New York
    • Bronx, New York, United States, 10451
      • Lincoln Hospital
    • Fresh Meadows, New York, United States, 11365
      • Queens Medical Associates
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10956
      • Hematology Oncology Associates of Rockland, PC
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Cancer Center
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation Hematology/Med Oncology
  • Oregon
    • Portland, Oregon, United States, 97201
      • Legacy Good Samaritan
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • SCOA-SC Onc Assoc
  • Texas
    • Houston, Texas, United States, 77030
      • VA Department of Hematology/Oncology
    • Richardson, Texas, United States, 75080
      • HOPE Oncology
    • Tyler, Texas, United States, 75701
      • Blood and Cancer Center of East Texas
    • Tyler, Texas, United States, 75701
      • Tyler Hematology/Oncology
  • Vermont
    • White River Junction, Vermont, United States, 05009
      • Veterans Administration Medical Center
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Virginia Oncology Associates Research Program
  • Washington
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology/Oncology
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Morgantown Internal Medicine Group

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:

• Unresectable, stage IIIA or IIIB NSCLC (measurable disease is not required)
• No evidence of metastatic disease
• No prior treatment
• Adequate organ function
• Adequate pulmonary function (FEV >= 1.0L or predicted FEV >0.8L)

Exclusion Criteria:

• Metastasis
• Prior treatment
• Malignant pleural or pericardial effusion
• Peripheral neuropathy >= grade 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Erlotinib (Tarceva) 150mg: Erlotinib 150mg orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events, death or completion of 3 years of therapy.	Drug: Erlotinib (tarceva); Erlotinib 150mg orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events, death or completion of 3 years of therapy.
PLACEBO_COMPARATOR: 2; Matched Placebo: Matched placebo orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events death or completion of 3 years of therapy.	Drug: Placebo; Matched placebo orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events death or completion of 3 years of therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival is defined as time from randomization until documented disease progression or death from any cause. The Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.0) was used to determine disease progression. Irradiated target lesions were considered non-measurable disease. Symptomatic radiographic changes of irradiated non-measurable disease required pathologically confirmation or positive FDG-PET scan 6 months following completion of concurrent chemoradiation to be considered locoregional disease progression. Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression was considered distant disease progression.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		From date of randomization until the date of death from any cause, assessed up to 50 months
Percent of Participants Surviving 3 Years		36 months
Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation	Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized.	18 months
Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo	Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized.	18 months

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: Sanofi; Genentech, Inc.
• Investigators: Study Chair: James R Rigas, MD, Norris Cotton Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (ESTIMATE): September 12, 2005

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 4, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Erlotinib; Web based; Tarceva; Stage III NSCLC
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: D-0410