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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
Results First Received: April 2, 2014  
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
Condition: Non-small Cell Lung Cancer
Interventions: Drug: Erlotinib
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients with stage IB to IIIA epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) were enrolled globally. 1252 patients were enrolled however 2 patients did not have adequate Health Insurance Portability and Accountability Act (HIPAA) documentation and were removed from the database.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants randomized prior to 7 November 2007 comprise the Breached-Protocol Cohort (BPC); those who had not discontinued were offered open-label erlotinib for up to 2 years. Participants randomized subsequently are referred to as the Randomized Cohort.

Reporting Groups
  Description
RC: Erlotinib Participants in the randomized cohort (RC) who 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.
RC: Placebo Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
BPC-NOLC: Erlotinib/Placebo The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib.
BPC-NOLC: Placebo Only The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib.
BPC-OLC: Erlotinib The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period.

Participant Flow:   Overall Study
    RC: Erlotinib     RC: Placebo     BPC-NOLC: Erlotinib/Placebo     BPC-NOLC: Placebo Only     BPC-OLC: Erlotinib  
STARTED     623     350     134     11     132  
Received Treatment     612     342     134     7     132  
COMPLETED     253 [1]   197 [1]   0 [1]   0 [1]   60 [1]
NOT COMPLETED     370     153     134     11     72  
Relapse of NSCLC                 116                 104                 19                 2                 26  
Adverse Event                 191                 22                 59                 0                 34  
Patient request                 36                 18                 43                 6                 7  
Medical/ethical/noncompliance reason                 20                 9                 10                 2                 5  
Death                 7                 0                 3                 1                 0  
[1] Completed 2 years of study treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
RC: Erlotinib Participants in the randomized cohort (RC) who 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.
RC: Placebo Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
BPC-NOLC: Erlotinib/Placebo The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib.
BPC-NOLC: Placebo Only The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib.
BPC-OLC: Erlotinib The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period.
Total Total of all reporting groups

Baseline Measures
    RC: Erlotinib     RC: Placebo     BPC-NOLC: Erlotinib/Placebo     BPC-NOLC: Placebo Only     BPC-OLC: Erlotinib     Total  
Number of Participants  
[units: participants]
  623     350     134     11     132     1250  
Age  
[units: years]
Mean ± Standard Deviation
           
Randomized Cohort     62.0  ± 9.28     61.8  ± 9.34     NA  ± NA [1]   NA  ± NA [1]   NA  ± NA [1]   61.9  ± 9.30  
Breached Protocol Cohort, No Open label     NA  ± NA [2]   NA  ± NA [2]   64.4  ± 9.33     62.7  ± 6.23     NA  ± NA [2]   64.3  ± 9.13  
Breached Protocol Cohort, Open label     NA  ± NA [3]   NA  ± NA [3]   NA  ± NA [3]   NA  ± NA [3]   61.8  ± 9.35     61.8  ± 9.35  
Gender  
[units: participants]
           
Female     257     141     47     2     57     504  
Male     366     209     87     9     75     746  
Race/Ethnicity, Customized  
[units: participants]
           
White     500     279     114     10     111     1014  
Black     14     11     4     0     4     33  
Asian     107     60     15     1     17     200  
American Indian/Alaska Native     1     0     1     0     0     2  
Other     1     0     0     0     0     1  
Race/Ethnicity, Customized  
[units: participants]
           
Not Hispanic or Latino     583     322     123     11     124     1163  
Hispanic or Latino     40     28     11     0     8     87  
Eastern Cooperative Oncology Group (ECOG) Performance Status [4]
[units: participants]
           
Grade 0     385     211     75     5     77     753  
Grade 1     230     134     55     6     54     479  
Grade 2     6     5     3     0     1     15  
Not measured     2     0     1     0     0     3  
Cigarette Smoking History  
[units: participants]
           
Never smoked or ≤ 100 cigarettes in lifetime     129     70     19     1     19     238  
Former smoker     423     240     103     9     104     879  
Current smoker     71     40     12     1     9     133  
Histology  
[units: participants]
           
Adenocarcinoma     367     211     73     3     76     730  
Squamous cell carcinoma     196     111     48     8     49     412  
Undifferentiated large cell     22     8     6     0     4     40  
Mixed NSCLC     29     18     5     0     1     53  
Other     9     2     2     0     2     15  
Extent of Disease at Diagnosis [5]
[units: participants]
           
Stage IA     1     2     1     0     0     4  
Stage IB     329     167     64     4     80     644  
Stage IIA     42     24     10     1     9     86  
Stage IIB     155     99     36     4     23     317  
Stage IIIA     93     58     21     1     17     190  
Stage IIIB     2     0     2     0     3     7  
Stage IV     1     0     0     1     0     2  
Adjuvant Chemotherapy  
[units: participants]
           
Yes     315     200     63     5     68     651  
No     308     150     71     6     64     599  
Epidermal Growth Factor Receptor (EGFR) Mutation Status [6]
[units: participants]
           
Activating mutation-positive     102     59     10     0     16     187  
Wild-type     458     245     116     11     107     937  
Undetermined     29     16     1     0     1     47  
Activating mutation not positive     30     27     5     0     6     68  
Not Available     4     3     2     0     2     11  
EGFR Gene Amplification [7]
[units: participants]
           
Positive     445     255     84     8     100     892  
Negative     167     87     49     3     32     338  
Undetermined     11     8     1     0     0     20  
[1] Randomized Cohort only
[2] Breached Protocol Cohort - No Open Label only
[3] Breached Protocol Cohort - Open Label only
[4] ECOG criteria: 0: Fully active. 1: Ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of all selfcare. 3: Capable of limited selfcare, confined to bed or chair more than 50% of waking hours. 4: Completely disabled, no selfcare, totally confined to bed or chair. 5: Dead.
[5] Staging is based on the size of the main tumor and whether it has grown into nearby areas, the spread of cancer to nearby lymph nodes and whether the cancer has spread (metastasized) to other organs of the body.
[6]

EGFR mutation status:

Activating mutation-positive: exon 19 deletion or exon 21 L858R (or both) detected.

Wild-type: neither exon 19 deletion nor exon 21 L858R or any other mutation (exon 18, 19, 20 and 21) detected or undetermined.

Undetermined: exon 19 deletion or exon 21 L858R (or both) mutation status undetermined.

Activating mutation not positive: neither exon 19 deletion nor exon 21 L858R detected or undetermined (includes other mutation positive and other mutation status undetermined).

[7] Analysis of tumor tissue by fluorescent in situ hybridization (FISH), positivity was defined as amplification (EGFR gene to chromosome ratio of ≥ 2 or ≥ 15 EGFR gene copies in ≥ 10% of tumor cells) or high polysomy (≥ 4 EGFR gene copies in ≥ 40% of tumor cells) .



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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). ]

2.  Secondary:   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) ]

3.  Secondary:   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). ]

4.  Secondary:   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) ]

5.  Secondary:   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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Company makes no warranties or representations of any kind as to the currency or completeness of the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose and shall not be liable for any damages.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Senior Medical Director, Medical Oncology
Organization: Astellas Pharma Global Development, Inc.
e-mail: clinicaltrial.disclosure@us.astellas.com


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