Personalized Therapy in Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Excision repair cross complementing 1 (ERCC1) ribonucleotide reductase M1 (RRM1) and thymidylate synthase(TS) are molecular determinants that predict sensitivity or resistance to platinum agents 、 gemcitabine and pemetrexed respectively. Tailored therapy using these molecular determinants suggested patient benefit in a previously reported phase 2 trial. Here, we designed a study for an individual patient analysis of prospectively accrued patients who were treated with the personalized therapy approach versus other standard approaches.

Detailed Description
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Patients who had nonsmall- cell lung cancer (NSCLC) performance status of 0/1 were accrued to 2 phase 2 clinical trials Trial A (carboplatin and chemotherapy individuation based on sensitivity marker ), Trial B (carboplatin non-individuation or chemotherapy non-individuation ). Patients who were treated on Trials B were analyzed as the standard therapy group. Patients accrued to Trial A were called the personalized therapy group. disease free survival (DFS) was estimated using the Kaplan-Meier method.

Official Title
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The Clinical Study of Personalized Therapy for Non-small Cell Lung Cancer Based on ERCC1/RRM1/TS Expression

Conditions
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Lung Cancer, Carboplatin Adverse Reaction

Intervention / Treatment
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* Drug: carboplatin, gemcitabine , pametrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed non-small cell lung cancer age from 18 years to 75 years ECOG Performance Status no more than 2 at least one appraisable lung focus of diameter≥ 10 mm by lung CT Haemoglobin ≥10.0 g/dl, Absolute neutrophil count ≥(ANC) 1.5 x 109/L, platelets ≥100 x 109/L Total bilirubin ≤1.5 x upper limit of normal (ULN) ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases Creatinine clearance ≥60ml/min (calculated according to Cockcroft-gault formula) Informed consent should be obtained before treatment. Exclusion Criteria: Mixed non-adenocarcinoma cell lung cancer histology Previous treatment for Systemic chemotherapy or local radiotherapy Be allergic to chemotherapy drugs second active primary malignancy or serious concomitant medical disease difficulties with adequate follow-up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A.individual therapy<br>Carboplatin was administrated at an area under the plasma concentration time curve (AUC) of 5 on day 1 every 21 days, while gemcitabine was administrated at a dose of 1250 mg/m2 on day 1 and 8 and pemetrexed was administrated at a dose of 500 mg/m2 on day 1. | Drug: carboplatin, gemcitabine , pametrexed<br>* A.individual therapy :enrolled patients with ERCC1 negative tumors who received carboplatin and a third-generation agent (gemcitabine or pametrexed) based on RRM1 or TS expression. If RRM1 protein was negatively expressed in the tumor tissues, gemcitabine was used, whereas pemetrexed was used if RRM1 was positively expressed and TS was negatively expressed. B.non-individualized therapy :enrolled patients who received carboplatin and a third-generation agent but were not based on ERCC1, RRM1, or TS expression.<br>|
| Experimental: B. non-individualized therapy<br>Carboplatin was administrated at an area under the plasma concentration time curve (AUC) of 5 on day 1 every 21 days, while gemcitabine was administrated at a dose of 1250 mg/m2 on day 1 and 8 and pemetrexed was administrated at a dose of 500 mg/m2 on day 1. | Drug: carboplatin, gemcitabine , pametrexed<br>* A.individual therapy :enrolled patients with ERCC1 negative tumors who received carboplatin and a third-generation agent (gemcitabine or pametrexed) based on RRM1 or TS expression. If RRM1 protein was negatively expressed in the tumor tissues, gemcitabine was used, whereas pemetrexed was used if RRM1 was positively expressed and TS was negatively expressed. B.non-individualized therapy :enrolled patients who received carboplatin and a third-generation agent but were not based on ERCC1, RRM1, or TS expression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The disease-free survival | The disease-free survival was measured from the day of tumor resection until tumor recurrence (progression) or death as the end point | Followed up these patients for disease-free survival for 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, gemcitabine, carboplatin, pemetrexed