Chemotherapy With Pemetrexed in Combination With Platinum for Advanced Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This is a two-arm, parallel, open-label, Phase 2 multicenter study of pemetrexed as first line combination therapy with either cisplatin or carboplatin in the palliative setting of stage IIIb and IV non-small cell lung cancer patients. Approximately 130 patients will be included in about 15 centers in Germany and randomized to one of the above treatment regimens in a 1:1 ratio. Chemotherapy will be administered over a maximum of six cycles with a standard length of 21 days. Primary objective will be the Progression Free Survival Time of patients as assessed in both treatment arms.

Official Title
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A Randomized Phase 2 Study of Pemetrexed in Combination With Cisplatin or Carboplatin in the First Line Therapy of Advanced NSCLC

Conditions
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Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically and/or histologically confirmed NSCLC Stage IIIb or IV No previous systemic chemotherapy for this cancer At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria In Solid Tumors (RECIST) criteria Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1 and adequate organ function Prior radiation therapy allowed but limited to <25% of the patient's bone marrow Exclusion Criteria: Serious concomitant systemic disorder or active infection Mild to moderate renal insufficiency, but unable to interrupt salicylates or other nonsteroidal anti-inflammatory drugs Symptomatic central nervous system (CNS) metastases requiring concurrent corticosteroid therapy Presence of clinically significant third-space fluid collections

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed + Cisplatin<br> | Drug: Pemetrexed<br>* 500 mg/m2, intravenous (IV), every 21 days x 6 cycles<br>* Other names: Alimta;Drug: Cisplatin<br>* 75 mg/m2, intravenous (IV), every 21 days x 6 cycles<br>|
| Experimental: Pemetrexed + Carboplatin<br> | Drug: Pemetrexed<br>* 500 mg/m2, intravenous (IV), every 21 days x 6 cycles<br>* Other names: Alimta;Drug: Carboplatin<br>* Area under the concentration curve (AUC) 5, intravenous (IV), every 21 days x 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Surviving Progression-Free at 6 Months (Progression Free Survival [PFS] Rate) | For this study, we used the exponential distribution (assumption done for the calculation of the sample size) to estimate the PFS rate. The PFS rate (%) and the 95% confidence intervals were calculated based on the following formula: exp(-6 λ) ± 1.96 * exp(-6 λ) * (-6 λ)/√r. Where λ was calculated based on the Maximum-Likelihood estimator for ln(λ) as given by (Collett 2003): ln(λ) = ln[ r / ∑ti ] with r = number of patients with events up to 6 months, ti = survival time of patient i (i=1,…,n), event or censored up to 6 months, and n= total number of patients per treatment group. | Randomization to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time from randomization to the date of death from any cause. | Randomization to date of death from any cause (up to 1 year) | 
| Number of Participants With Tumor Response (as Basis for Response Rate) | Best overall response was evaluated using RECIST Criteria which define when cancer patients improve (respond), stay the same (stabilize), or worsen (progression) during treatment. CR: complete response, disappearance of all target lesions; PR: partial response, 30% decrease in sum of the longest diameter of target lesions; PD: progressive disease, 20% increase in sum of the longest diameter of target lesions; SD: stable disease, small changes not meeting above criteria. Response Rate: number of participants with response(CR+PR)per total population, multiplied by 100 to give a percentage. | Every 6 weeks for 6 months during the treatment period, and every 3 months during the follow-up period, until disease progression | 
| Time to Treatment Failure (TTF) | Defined as time from randomization to the first date of disease progression, death due to any cause, or early discontinuation of treatment (any reason), whichever occurred first | Randomization to stopping of treatment, progression, death or initiation of further chemotherapy, whichever occurs first (up to 1 year) | 
| Pharmacology Toxicities | Number of patients experiencing Grade 3 or 4 hematologic and non-hematologic adverse events (AEs) possibly related to study drug or protocol procedures in this study (a subset of those listed in the AE Module). AEs were graded using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) for defining and grading specific adverse events. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death). Grade 3 AEs are severe and undesirable; Grade 4 AEs are life-threatening or disabling. | Every 21-day cycle for up to 6 cycles |