Molecular Profiling in Lung Cancer Patients

Study Overview
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Brief Summary
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The main purpose of this study of pemetrexed combined with cisplatin used as neoadjuvant chemotherapy (2 or 3 cycles) in participants with operable non-small cell lung cancer (NSCLC) is to look at various genes present in participants' blood and tumor tissue to see if there is any link between the levels or changes in the genes and how participants with lung cancer respond to pemetrexed and cisplatin treatment.

Official Title
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Molecular Profiling and Safety Study of Operable Lung Cancer Patients Treated With Alimta Combined With Cisplatin as Neoadjuvant Chemotherapy

Conditions
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Non-Small Cell Lung Cancer, Carcinoma

Intervention / Treatment
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* Drug: pemetrexed
* Drug: cisplatin
* Procedure: Radical Non-Small Cell Lung Cancer (NSCLC) surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pathologic documentation of non-small cell lung cancer (NSCLC) tumor must be accessible by bronchoscopy for tumor tissue sample collection patients must have lung cancer with clinical stage IB, II, IIIA Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 patients must not have received prior systemic chemotherapy or radiation therapy for NSCLC (prior resection of lung is allowed provided at least 5 years have elapsed between prior surgery and enrolment) Exclusion Criteria: bronchoalveolar carcinoma or stage IIIA tumor involving the superior sulcus (Pancoast tumors) pregnant or breast feeding patients patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry patients with history or presence of other malignancy except in situ carcinoma of the skin or prior malignancy treated more than 5 years before without recurrence (excluding melanoma, breast cancer and hypernephroma) unwillingness to take folic acid or vitamin B12 supplementation

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed + Cisplatin<br>Pemetrexed: 500 milligrams per square meter (mg/m^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs Cisplatin: 75 mg/m^2 IV q 21 days for 3 cycles unless disease progression occurs | Drug: pemetrexed<br>* 500 mg/m^2 IV q 21 days for 3 cycles unless disease progression occurs<br>* Other names: Alimta;Drug: cisplatin<br>* 75 mg/m^2 IV q 21 days for 3 cycles unless disease progression occurs<br>Procedure: Radical Non-Small Cell Lung Cancer (NSCLC) surgery<br>* All participants proceeded to surgery within 4-8 weeks from the last dose of pemetrexed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High/Low Expression of Selected Molecular Markers in Tumor Tissues and Hypermethylated Genes in Peripheral Blood | Molecular markers assessed by immunohistochemistry: thymidylate synthase, glycinamide ribonucleotide formyl transferase (GARFT), epidermal growth factor receptor (EGFR); and by polymerase chain reaction: dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthetase (FPGS), reduced folate carrier, alpha folate receptor, Excision Repair Cross-Complementation Group 1 (ERCC1), folylpolyglutamate hydrolase (FPGH). Hypermethylated genes assessed by methylation-specific polymerase chain reaction. Due to small sample size, tumor-tissue analyses were not done. | Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Tumor Response (Response Rate) | Tumor response to treatment using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Response rate was estimated as the total number of CR or PR, divided by the total number of participants treated. | Treatment start to disease progression or surgery (4-8 weeks after last dose of pemetrexed) | 
| Duration of Response | The duration of response was defined as the time from complete response (CR) or partial response (PR) to disease progression. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions. | Time of response to disease progression (up to 44.4 months) | 
| Disease Free Survival (DFS) | DFS was the time from date of first dose to first observation of progressive disease (PD) or death due to any cause. PD=20% increase in sum of longest diameter of target lesions. If a participant was not known to have died or have PD, DFS was censored at the date of the last objective progression-free disease assessment. | Treatment start to disease progression or death from any cause (up to 45.5 months) | 
| Overall Survival (OS) | OS was defined as the time from treatment start to death from any cause. For participants who were alive, OS was censored at the last contact date. | Treatment start to death from any cause (up to 47.6 months) |