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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: September 1, 2015
Last verified: September 2015
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                35                18                43                6                7 
Medical/ethical/noncompliance reason                21                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 
Overall Participants Analyzed 
[Units: Participants]
 623   350   134   11   132   1250 
Age [1] [2] [3] 
[Units: Years]
Mean (Standard Deviation)
           
Randomized Cohort   62.0  (9.28)   61.8  (9.34)   NA [1]   NA [1]   NA [1]   61.9  (9.30) 
Breached Protocol Cohort, No Open label   NA [2]   NA [2]   64.4  (9.33)   62.7  (6.23)   NA [2]   64.3  (9.13) 
Breached Protocol Cohort, Open label   NA [3]   NA [3]   NA [3]   NA [3]   61.8  (9.35)   61.8  (9.35) 
[1] Randomized Cohort only
[2] Breached Protocol Cohort - No Open Label only
[3] Breached Protocol Cohort - Open Label only
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 [1] 
[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 
[1] 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.
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 [1] 
[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 
[1] 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.
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 [1] 
[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 
[1]

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).

EGFR Gene Amplification [1] 
[Units: Participants]
           
Positive   445   255   84   8   100   892 
Negative   167   87   49   3   32   338 
Undetermined   11   8   1   0   0   20 
[1] 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 until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months). ]

2.  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 until the data cutoff date of 11 June 2014 (maximum time on follow-up was 78 months). ]

3.  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 until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months). ]

4.  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 until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months). ]

5.  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 until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months). ]

6.  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 until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months). ]

7.  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 until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months) ]

8.  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 until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months) ]

9.  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. Data are based off the 11 June 2014 data cut-off date. ]


  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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Astellas Pharma Inc ( OSI Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00373425     History of Changes
Other Study ID Numbers: OSI-774-302
2005-001747-29 ( EudraCT Number )
Study First Received: September 7, 2006
Results First Received: April 2, 2014
Last Updated: September 1, 2015
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