Pemetrexed/Cisplatin Versus Gemcitabine/Cisplatin According to Thymidylate Synthase Expression

Study Overview
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Brief Summary
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This study trys to evaluate the predictive role of thymidylate synthase expression for pemetrexed/cisplatin in Non-small Cell Lung Cancer (NSCLC).

Official Title
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A Randomized Phase II Study Comparing Pemetrexed Plus Cisplatin With Gemcitabine Plus Cisplatin According to Thymidylate Synthase Expression in Non-squamous Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Gemcitabine plus cisplatin
* Drug: pemetrexed plus cisplatin
* Drug: pemetrexed plus cisplatin
* Drug: Gemcitabine plus cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed nonsquamous NSCLC Stage IIIb, IV or recurrent NSCLC Age ≥ 18years ECOG performance status of 0 to 1 Known TS immunohistochemical analysis data At least one measurable lesion by RECIST 1.1 No previous chemotherapy or therapy with EGFR TKIs for advanced NSCLC Asymptomatic brain metastasis or symptomatic brain metastasis treated with local treatment such as operation, whole brain radiotherapy, or gamma-knife surgery At least 2 weeks later after whole brain radiotherapy or palliative radiotherapy Adequate renal function: estimated creatinine clearance ≥ 50mL/min Exclusion Criteria: Patients whose disease recurred within 6 months after the completion of adjuvant chemotherapy. Patients with post-obstructive pneumonia or uncontrolled serious infection

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: TS positive cohort & Gem/Cis Tx arm<br>Among TS expression positive patients, some will be randomized to Gem/cis therapy | Drug: Gemcitabine plus cisplatin<br>* Gemcitabine 1000mg/m2 D1, D8 & cisplatin 70mg/m2 D1 every 3 weeks<br>|
| Active Comparator: TS+ cohort & Pem/Cis arm<br>Among patients with TS+, randomised to Pem/cis chemotherapy | Drug: pemetrexed plus cisplatin<br>* Pemetrexed 500mg/m2 & cisplatin 70mg/m2 D1 every 3 weeks<br>|
| Active Comparator: TS negative cohort & Pem/Cis Tx arm<br>Among patients with TS-, some will be randomised to Pem/cis Tx arm | Drug: pemetrexed plus cisplatin<br>* pemetrexed 500mg/m2 & cisplatin 70mg/m2 every 3 weeks<br>|
| Experimental: TS negative cohort & Gem/Cis Tx arm<br>Among patients with TS-, some will be randomised to Gem/Cis Tx arm | Drug: Gemcitabine plus cisplatin<br>* Gemcitabine 1000mg/m2 D1, D8 & cisplatin 70mg/m2 D1 every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| predictive value of TS expression | To determine the predictive value of thymidylate synthase expression in NSCLC patients treated with pemetrexed combination therapy by interaction P value | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate | Whether the response rate of CG regimen is higher than that of CP regimen in TS+ patients | 12 months | 
| response rate | Whether the response rate of CP regimen is higher than that of CG regimen in TS- patients | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thymidylate synthase