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Feasibility Study of Pemetrexed in Combination With Cisplatin or Carboplatin as Adjuvant Treatment of Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00269152
First received: December 21, 2005
Last updated: December 6, 2011
Last verified: December 2011
History of Changes
Results First Received: November 12, 2008  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Non-Small Cell Lung Cancer
Interventions: Drug: pemetrexed
Drug: cisplatin
Drug: carboplatin

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles
Pemetrexed + Carboplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Carboplatin: area under the curve (AUC) 5 mg/ml*min, intravenous (IV), every 21 days x 4 cycles

Participant Flow:   Overall Study
    Pemetrexed + Cisplatin     Pemetrexed + Carboplatin  
STARTED     63 [1]   59 [2]
COMPLETED     45     49  
NOT COMPLETED     18     10  
Adverse Event                 9                 3  
Withdrawal by Subject                 7                 3  
Physician Decision                 2                 3  
Protocol Violation                 0                 1  
[1] One patient in Pemetrexed+Carboplatin actually received Pemetrexed+Cisplatin
[2] 4 were randomized without receiving any study drug.



  Baseline Characteristics
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Reporting Groups
  Description
Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles
Pemetrexed + Carboplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Carboplatin: area under the curve (AUC) 5 mg/ml*min, intravenous (IV), every 21 days x 4 cycles
Total Total of all reporting groups

Baseline Measures
    Pemetrexed + Cisplatin     Pemetrexed + Carboplatin     Total  
Number of Participants  
[units: participants]
 		  63     59     122  
Age  
[units: years]
Mean ± Standard Deviation 		  60.6  ± 7.7     58.9  ± 7.2     59.7  ± 7.5  
Gender  
[units: participants]
 		     
Female     14     18     32  
Male     49     41     90  
Race/Ethnicity, Customized  
[units: participants]
 		     
Caucasian     62     58     120  
African     1     1     2  
Region of Enrollment  
[units: participants]
 		     
France     12     8     20  
Spain     7     8     15  
Germany     44     43     87  
Curative Surgery Used  
[units: participants]
 		     
Pneumonectomy     9     9     18  
Lobectomy     46     46     92  
Bi-lobectomy     8     4     12  
Smoking History  
[units: participants]
 		     
Yes     56     56     112  
No     7     3     10  
Stage of Disease Prior to Tumor Resection [1]
[units: participants]
 		     
Stage Ia     0     1     1  
Stage Ib     27     26     53  
Stage IIa     6     5     11  
Stage IIb     30     25     55  
Stage IIIa     0     1     1  
Unknown: could have been either Stage IIIb or IV     0     1     1  
Tumor Type at Initial Pathological Diagnosis  
[units: participants]
 		     
Adenocarcinoma of the Lung     27     23     50  
Squamous Carcinoma of the Lung     24     20     44  
Non-Small Cell Lung Cancer     5     4     9  
Mixed Cell (Squamous/Adeno) Carcinoma of Lung     0     5     5  
Large Cell Carcinoma of Lung     5     7     12  
Bronchoalveolar Carcinoma     2     0     2  
[1] Classification based on the American Joint Committee on Cancer Staging Criteria for Lung Cancer.



  Outcome Measures
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1.  Primary:   The Feasibility of Post-Surgery Chemotherapy   [ Time Frame: every 21-day cycle for 4 cycles up to 30 days after last infusion ]

Measure Type Primary
Measure Title The Feasibility of Post-Surgery Chemotherapy
Measure Description Feasibility was measured by completion of 4 treatment cycles without remaining toxicities >=Grade 3 at 30 days after last infusion.
Time Frame every 21-day cycle for 4 cycles up to 30 days after last infusion  
Safety Issue Yes  

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.
Number of patients in safety population, that is, number of patients enrolled, randomized and treated with at least one dose of study drug (presented by treatment received arm).

Reporting Groups
  Description
Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles
Pemetrexed + Carboplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Carboplatin: area under the curve (AUC) 5 mg/ml*min, intravenous (IV), every 21 days x 4 cycles

Measured Values
    Pemetrexed + Cisplatin     Pemetrexed + Carboplatin  
Number of Participants Analyzed  
[units: participants]
 		  64     54  
The Feasibility of Post-Surgery Chemotherapy  
[units: participants]
 		   
Patients "feasible"     38     27  
Non-feasible = Early Discontinuation     18     6  
Non-feasible = Lost to Follow-up     1     2  
Non-feasible = Remaining Grade 3/4 Toxicity     4     3  
Non-feasible = Underdosage (<95% intended dose)     5     19  


Statistical Analysis 1 for The Feasibility of Post-Surgery Chemotherapy
Groups [1] Pemetrexed + Cisplatin
Feasibility Response Rate (percentage) [2] 59.4
95% Confidence Interval ( 46.4 to 71.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for The Feasibility of Post-Surgery Chemotherapy
Groups [1] Pemetrexed + Carboplatin
Feasibility Response Rate (percentage) [2] 50.0
95% Confidence Interval ( 36.1 to 63.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



2.  Secondary:   Grade III/IV Adverse Events   [ Time Frame: every 21-day cycle for 4 cycles ]

Measure Type Secondary
Measure Title Grade III/IV Adverse Events
Measure Description Number of patients experiencing Grade III/IV hematologic and non-hematologic adverse events possibly related to study drug or protocol procedures in this study.
Time Frame every 21-day cycle for 4 cycles  
Safety Issue Yes  

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.
Number of patients in safety population, that is, number of patients enrolled, randomized and treated with at least one dose of study drug (presented by treatment received arm).

Reporting Groups
  Description
Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles
Pemetrexed + Carboplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Carboplatin: area under the curve (AUC) 5 mg/ml*min, intravenous (IV), every 21 days x 4 cycles

Measured Values
    Pemetrexed + Cisplatin     Pemetrexed + Carboplatin  
Number of Participants Analyzed  
[units: participants]
 		  64     54  
Grade III/IV Adverse Events  
[units: participants]
 		   
Neutropenia     9     6  
Anaemia     0     3  
Thrombocytopenia     0     3  
Febrile neutropenia     0     2  
Leukopenia     0     1  
Lymphopenia     1     0  
Neutrophil count decreased     1     6  
Haemoglobin count decreased     0     2  
Platelet count decreased     1     1  
White blood cell count decreased     0     2  
Asthenia     4     2  
Nausea     3     0  
Vomiting     3     0  
Fatigue     0     2  
Catheter related infection     1     0  
Gamma-glutamyltransferase increased     1     0  
Anorexia     1     0  
Hyperglycaemia     1     0  
Hyperkalaemia     1     0  
Psychotic disorder     1     0  

No statistical analysis provided for Grade III/IV Adverse Events



3.  Secondary:   Overall Survival at 3 Years   [ Time Frame: baseline to date of death from any cause, assessed at 3 years ]

Measure Type Secondary
Measure Title Overall Survival at 3 Years
Measure Description For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year survival rate. Results are presented as probability (%) of survival at 3 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date.
Time Frame baseline to date of death from any cause, assessed at 3 years  
Safety Issue Yes  

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.
All randomized participants. Intent to treat population.

Reporting Groups
  Description
Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles
Pemetrexed + Carboplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Carboplatin: area under the curve (AUC) 5 mg/ml*min, intravenous (IV), every 21 days x 4 cycles

Measured Values
    Pemetrexed + Cisplatin     Pemetrexed + Carboplatin  
Number of Participants Analyzed  
[units: participants]
 		  63     59  
Overall Survival at 3 Years  
[units: probability of survival (%)]
Number ( 95% Confidence Interval ) 		  81.9  
  ( 72.2 to 91.6 )   		  83.2  
  ( 73.2 to 93.2 )  

No statistical analysis provided for Overall Survival at 3 Years



4.  Secondary:   3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years   [ Time Frame: length of time disease free, assessed at 3 years ]

Measure Type Secondary
Measure Title 3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years
Measure Description For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year disease-free rate. Disease-free survival is defined as the time from enrollment to the first observation of disease progression, or death due to any cause. For participants not known to have died and to have had recurrent disease, disease-free survival was censored at the date of the last participant contact with No Recurrence status. Results are presented as probability (%) of disease-free survival at 3 years.
Time Frame length of time disease free, assessed at 3 years  
Safety Issue No  

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.
All randomized participants. Intent to Treat population.

Reporting Groups
  Description
Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles
Pemetrexed + Carboplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles Carboplatin: area under the curve (AUC) 5 mg/ml*min, intravenous (IV), every 21 days x 4 cycles

Measured Values
    Pemetrexed + Cisplatin     Pemetrexed + Carboplatin  
Number of Participants Analyzed  
[units: participants]
 		  63     59  
3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years  
[units: probability of disease-free survival (%)]
Number ( 95% Confidence Interval ) 		  61.2  
  ( 48.3 to 74.0 )   		  67.3  
  ( 54.5 to 80.1 )  

No statistical analysis provided for 3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years



5.  Secondary:   Overall Survival at 6 Years   [ Time Frame: baseline to date of death from any cause, assessed up to 6 years after the last participant was randomized ]
Results not yet posted.   Anticipated Posting Date:   07/2014   Safety Issue:   Yes


  Serious Adverse Events
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  Other Adverse Events
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  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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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
A protocol amendment was approved after the trial original completed to allow for collection of additional overall survival data due to number of participants surviving at 3 years.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 1-800-545-5979


No publications provided


Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00269152     History of Changes
Other Study ID Numbers: 10105, H3E-SB-S089
Study First Received: December 21, 2005
Results First Received: November 12, 2008
Last Updated: December 6, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices