A Study of Erlotinib (Tarceva) After Surgery With or Without Adjuvant Chemotherapy in Non-Small Cell Lung Carcinoma (NSCLC) Patients Who Have Epidermal Growth Factor Receptor (EGFR) Positive Tumors (RADIANT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( OSI Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00373425
First received: September 7, 2006
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

This is a study to evaluate the effectiveness of erlotinib compared with a placebo sugar pill following complete surgical removal of the tumor with or without chemotherapy after surgery in Stage IB-IIIA NSCLC patients.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Erlotinib
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Single-agent Tarceva® (Erlotinib) Following Complete Tumor Resection With or Without Adjuvant Chemotherapy in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma Who Have EGFR-positive Tumors

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Disease Free Survival (DFS) [ Time Frame: Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter (maximum time on follow-up was 64 months). ] [ Designated as safety issue: No ]
    DFS is the time from the date of randomization until the first day non-small cell lung cancer (NSCLC) relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter (maximum time on follow-up was 64 months) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.

  • Disease-free Survival in Participants With EGFR Mutation - Positive Tumors [ Time Frame: Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter (maximum time on follow-up was 64 months). ] [ Designated as safety issue: No ]
    Disease-free survival (DFS) is the time from the date of randomization until the first day NSCLC relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.

  • Overall Survival in Participants With EGFR Mutation - Positive Tumors [ Time Frame: Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter (maximum time on follow-up was 64 months) ] [ Designated as safety issue: No ]

    Overall survival is defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.

    Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.


  • Number of Participants With Adverse Events (AEs) [ Time Frame: From the date of first dose of study drug until 30 days after the last dose. The median time on treatment was 11.9 months for erlotinib and 21.9 months for placebo. ] [ Designated as safety issue: No ]

    An AE was defined as any untoward medical occurrence in a study participant and did not necessarily have a causal relationship with study treatment.

    An AE was considered serious if it resulted in death, a life-threatening situation, inpatient hospitalization or prolongation of an existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a patient who received study drug or other important medical events.

    A drug-related AE was any AE with at least a possible relationship to study treatment as assessed by the investigator. Severity was graded by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v3.0, where Grade 1=Mild AE; Grade=2 Moderate AE; Grade 3=Severe AE; Grade 4=Life-threatening or disabling; Grade 5=Death related to AE.



Enrollment: 1252
Study Start Date: September 2006
Study Completion Date: June 2014
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Drug: Erlotinib
150 mg tablet
Other Names:
  • OSI-774
  • Tarceva
Placebo Comparator: Placebo
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Drug: Placebo
Placebo tablet

Detailed Description:

After the initiation of the study, the sponsor became aware of an error in the drug dispensing module of the interactive voice response such that most patients who were randomized prior to 07 November 2007 were dispensed the incorrect study drug at least once. Since the integrity of the data from these patients was seriously compromised, these patients were considered unevaluable for the protocol-specified analyses. These participants are referred to as the breached protocol cohort (BPC) and those still on study treatment at the time of the breach were offered the option of receiving open-label erlotinib for up to 2 years (including posttreatment and long-term follow-up assessments), not receiving open-label erlotinib but remaining in the study for posttreatment and long-term follow-up assessment, or withdrawing consent from treatment and further assessments. Participants who had discontinued study treatment prior to the breach were not offered open-label erlotinib and remained in long-term follow-up. Data from the BPC participants were analyzed separately and were not included in the assessments of primary or secondary endpoints in the randomized cohort and were not considered part of the primary analyses.The sample size for the randomized cohort was not changed due to the BPC and the data from RC and BPC were analyzed separately.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary tissue from patient's surgery must be epidermal growth factor receptor (EGFR)-positive by certain tests
  • Patients may have up to 4 cycles of chemotherapy after surgery
  • Complete removal of the tumor by surgery
  • Able to start drug under the following timelines:

    • 6 months from the day of surgery for patients who get chemotherapy
    • 3 months from the day of surgery for those who do not get chemotherapy
  • Confirmed diagnosis of Stage IB-IIIA NSCLC
  • Patients must be accessible for follow-up visits

Exclusion Criteria:

  • History of prior radiotherapy for NSCLC either before or after surgery
  • History of heart disease or uncontrolled heart arrhythmias within the previous year
  • History of poorly controlled gastrointestinal (GI) disorders that could affect the absorption of study drug
  • History of other cancer except certain skin or cervical cancers, patients who have had other cancer are eligible if they have remained disease free for at least 5 years
  • Patients who have received chemotherapy for NSCLC before surgery
  • Tumors with mixed histology of NSCLC and Small Cell Lung Cancer (SCLC). Patients with carcinoid tumors are not eligible.
  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: NCT00373425

  Show 295 Study Locations
Sponsors and Collaborators
OSI Pharmaceuticals
Investigators
Study Director: Medical Monitor Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( OSI Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00373425     History of Changes
Other Study ID Numbers: OSI-774-302, 2005-001747-29
Study First Received: September 7, 2006
Results First Received: April 2, 2014
Last Updated: July 15, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Federal Office for Safety in Health Care
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Korea: Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: FSI Scientific Center of Expertise of Medical Application
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan: Center for Drug Evaluation
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Adjuvant Non-small Cell Lung Cancer
Tarceva
Early-stage Lung Cancer
Adjuvant
RADIANT
NSCLC
EGFR-positive tumor
Stage IB Non-small Cell Lung Cancer
Stage II Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014