Study of Pemetrexed Versus Pemetrexed Plus Erlotinib as Treatment of Nonsquamous Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This is a multicenter, randomized, Phase 2, open label, parallel trial to evaluate an effect of pemetrexed alone on nonsquamous non-small cell lung cancer (NSCLC) in a second-line setting (such as progression-free survival [PFS], disease control rate, best response rate, time to treatment failure [TTTF], overall survival [OS] and 1-year survival rates) compared to pemetrexed plus erlotinib combination.

Official Title
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A Phase 2 Study of Pemetrexed Versus Pemetrexed Plus Erlotinib in Second-Line Treatment in Patients With Nonsquamous NSCLC

Conditions
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Histological or Cytological Diagnosis of Locally Advanced or Metastatic NSCLC of Nonsquamous Histology and Not Amenable to Curative Therapy.

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Erlotinib
* Drug: Pemetrexed
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of locally advanced or metastatic NSCLC that is of nonsquamous histology and not amenable to curative therapy. Failure of previous treatment with one prior platinum-based chemotherapy regimen. Good performance status. Adequate bone marrow reserve, renal and hepatic functions. Exclusion Criteria: Serious concomitant systemic disease. Inability to take oral medication. Inability or unwillingness to take vitamin supplementation and corticosteroids. Pregnancy / Breast-feeding. Treatment with certain medicines that prevent blood from clotting.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed (Nonsquamous)<br>Group of participants with non-small cell lung cancer (NSCLC) of nonsquamous histology who were assigned to Pemetrexed arm | Drug: Pemetrexed<br>* 500 mg/m² intravenous (iv) over 10 minutes on the first day of each 21-day cycle until disease progression (PD) or unacceptable toxicity<br>* Other names: Alimta;|
| Experimental: Pemetrexed + Erlotinib (Nonsquamous)<br>Group of participants with NSCLC of nonsquamous histology who were assigned to Pemetrexed + Erlotinib arm | Drug: Erlotinib<br>* 150 mg given orally (po), daily (QD), starting on the first day of the first cycle<br>* Other names: Tarceva;Drug: Pemetrexed<br>* 500 mg/m² iv over 10 minutes on the first day of each 21-day cycle until PD or unacceptable toxicity<br>* Other names: Alimta;|
| Experimental: Pemetrexed (Squamous)<br>Group of participants with NSCLC of squamous histology who were assigned to Pemetrexed arm | Drug: Pemetrexed<br>* 500 mg/m² iv over 10 minutes on the first day of each 21-day cycle until PD or unacceptable toxicity<br>* Other names: Alimta;|
| Experimental: Pemetrexed + Erlotinib (Squamous)<br>Group of participants with NSCLC of squamous histology who were assigned to Pemetrexed + Erlotinib arm | Drug: Pemetrexed<br>* 500 mg/m² iv over 10 minutes on the first day of each 21-day cycle until PD or unacceptable toxicity<br>* Other names: Alimta;Drug: Erlotinib<br>* 150 mg given po, QD, starting on the first day of the first cycle<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria using computed tomography (CT) or magnetic resonance imaging (MRI) for objective determination of progressive disease (PD: ≤20% increase in sum of longest diameter of target lesion). For participants alive as of data cut-off date who did not have PD, PFS was censored at date of last CT/MRI. For participants who received subsequent systemic anticancer therapy (after study discontinuation) prior to PD or death, PFS censored at date of last CT/MRI prior to initiation of post discontinuation systemic anticancer therapy. | Baseline to date of measured PD or death from any cause. Maximum follow-up was from baseline to 32.2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Best Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) (Disease Control Rate) | Per RECIST: CR: Disappearance of all target lesions; PR: Either a) ≤30% decrease in sum of longest diameter (LD) of target lesions or b) complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesions. In either case, no new lesions may have appeared. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD. PD: ≤20% increase in sum of LD of target lesions. Disease Control Rate (%) = (SD+PR+CR)/number of participants in arm*100. | Baseline to measured PD. Maximum follow-up was from Baseline to 34 months | 
| Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) (Response Rate) | CR: Disappearance of all tumor lesions; PR: Either a) at least a 30% decrease in sum of LD of target lesions or b) complete disappearance of target lesions, with persistence (but not worsening) ≥1 nontarget lesions. In either case, no new lesions may have appeared. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD. PD: ≤20% increase in the sum of LD of target lesions. Response Rate (%) = (CR+PR)/number of participants in arm*100. | Baseline to measured progressive disease. Maximum follow-up was from Baseline to 34 months | 
| Time to Treatment Failure (TTTF) | Defined as the time from randomization to death from any cause, first observation of PD, or study treatment discontinuation due to any reason other than protocol complete or satisfactory response. For participants who discontinued due to protocol complete or satisfactory response, or for participants not known to have discontinued as of the data cut-off date, TTTF was censored at the last contact date. | Baseline to first date among death from any cause, PD, or study treatment discontinuation for any reason other than protocol complete or satisfactory response. Maximum follow-up was from Baseline to 32.2 months | 
| Overall Survival (OS) | OS time is the duration from randomization to the date of death from any cause. For each participant who was not known to have died as of the data inclusion cut-off date, OS was censored at the date of last contact. | Baseline to date of death from any cause. Maximum follow-up was from Baseline to 42.6 months. | 
| Percentage of Participants Surviving at 1 Year | Overall Survival (OS) rate at 1 year from the date of randomization was determined using the distribution of OS times and was estimated using the Kaplan-Meier method. | Baseline to date of death from any cause up to 1 year | 
| Number of Participants With Adverse Events (AEs) | Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module. | Baseline up to 42.2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nonsquamous