Pemetrexed +/- Carboplatin as Second Line Treatment in NSCLC

Study Overview
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Brief Summary
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The aim of this study is to compare time to progression between the combination pemetrexed-carboplatin and pemetrexed alone in previously treated patients with locally advanced or metastatic NSCLC.

Detailed Description
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In spite of the superiority of single agent over best supportive care in second-line NSCLC, the prognosis of these patients remains poor with a median survival of 6-7 months, justifying the evaluation of new regimens in this setting. An open question in the second-line treatment of NSCLC remains the possible superiority of combination chemotherapy over single agent, as it has been clearly demonstrated in first-line. Particularly, the addition of platinum to either docetaxel or pemetrexed should be further investigated especially in patients with prior response/stable disease to platinum-based first-line chemotherapy. Pemetrexed has shown anti-tumor activity in combination with other chemotherapy agents, including gemcitabine, vinorelbine, taxanes, cisplatin and carboplatin. In this multicenter, open label, randomized phase II trial, pemetrexed 500 mg/m2 and carboplatin AUC 5 will be administered on day 1 every 3 weeks until progression of disease or for a maximum of 4 courses in the experimental arm. The control arm will be pemetrexed as single agent at 500 mg/m2 on day 1 every 3 weeks until progression of disease or for a maximum of 4 courses.

Official Title
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Randomized Phase II Study of Pemetrexed Versus Pemetrexed and Carboplatin as Second Line Chemotherapy in Advanced Non-small-cell Lung Cancer (NSCLC).

Conditions
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Advanced Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Pemetrexed plus carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent Histologically or cytologically confirmed non-small-cell lung cancer Unresectable stage IIIB, stage IV and unresectable local relapse or metastatic disease, with evidence of disease progression after first line chemotherapy which should have included a platinum agent. ECOG performance status lower than or equal to 2 Adequate hematological, hepatic and renal functions Life expectancy greater than or equal to 12 weeks Prior treatment with only 1 chemotherapy regimen for the treatment of advanced disease which should have included a platinum agent At baseline, presence of at least one measurable target lesion as per RECIST criteria Exclusion Criteria: Prior treatment with pemetrexed. Patients who are pregnant or lactating Patients with any underlying medical condition that might be aggravated by treatment or which cannot be controlled. Symptomatic brain metastases History of another malignancy within the past five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix. Concomitant treatment with any other anticancer drug.

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 |
| --- | --- |
| Active Comparator: A<br>Monochemotherapy | Drug: Pemetrexed<br>* Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 of a 21 days cycle<br>|
| Experimental: B<br>Combination chemotherapy | Drug: Pemetrexed plus carboplatin<br>* Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 and Carboplatin AUC 5 i.v. over approximately 30 minutes on day 1 (beginning approximately 30 minutes after the end of the pemetrexed infusion) of a 21 days cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare time to progression between the combination pemetrexed-carboplatin and pemetrexed alone in previously treated patients with locally advanced or metastatic NSCLC |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess differences in terms of response rate between the combination pemetrexed-carboplatin and pemetrexed alone. |  | 3 months | 
| To assess differences in terms of duration of response between the combination pemetrexed-carboplatin and pemetrexed alone. |  | 36 months | 
| To assess differences in terms of toxicity between the combination pemetrexed-carboplatin and pemetrexed alone. |  | 3 months | 
| To assess differences in terms of survival between the combination pemetrexed-carboplatin and pemetrexed alone. |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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second line treatment, pemetrexed, carboplatin