Pharmacogenomics IND EXEMPT SNP Clinical Study - Etoposide and Single Nucleotide Polymorphisms

Study Overview
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Brief Summary
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Explore the relationship between drug target topoisomerase II gene single nucleotide polymorphisms and Etoposide (VP-16) therapeutic-effects in patients with small cell lung cancer, based on Oxford precisely sequencing drug targets' genes. Explore the relationship between drug target CYP4503A4 gene single nucleotide polymorphisms and Etoposide (VP-16) side-effects in patients with small cell lung cancer, based on Oxford precisely sequencing drug targets' genes.

Detailed Description
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The usual approach group, after lung tissue biopsy, 300 double blind random group separated SCLC patients currently used the Combined Chemotherapy on Etoposide Injection, it will try to look for the relationship between the ETOPOSIDE therapeutic efficacy and the Topoisomerase II SNP Genotyping, and the relationship between the ETOPOSIDE therapeutic safety and the CYP4503A4 SNP Genotyping, based on Oxford precisely sequencing drug targets' genes. The study approach group, after lung tissue biopsy, 300 double blind random group separated SCLC patients currently used the Combined Chemotherapy on Etoposide Capsule, it will try to look for the relationship between the ETOPOSIDE therapeutic efficacy and the Topoisomerase II SNP Genotyping, and the relationship between the ETOPOSIDE therapeutic safety and the CYP4503A4 SNP Genotyping, based on Oxford precisely sequencing drug targets' genes. 1) Detect drug target whole gene precision sequence of everyone patient for all 600 recruited double blind SCLC patients. 2) Mutually compare everyone patient drug target whole gene precision sequence for a total of 600 recruited double blind SCLC patients. 3) Calculate drug target gene SNPs in all 600 recruited double blind SCLC patients. 4) Correlate everyone patient drug target gene SNP to everyone patient drug efficacy. 5) Correlate everyone patient drug target gene SNP to everyone patient drug safety. 6) Mutually compare the usual approach group SNPs (300 double blind random group separated SCLC patients) with the study approach group SNPs (300 double blind random group separated SCLC patients). 7) Confirm the relationship between drug target gene SNPs and drug efficacy. 8) Confirm the relationship between drug target gene SNPs and drug safety.

Official Title
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Explore the Relationship Between Single Nucleotide Polymorphisms and Etoposide Response and Toxicity in Patients With Small Cell Lung Cancer.

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: ETOPOSIDE - Usual
* Drug: ETOPOSIDE - Study


Participation Criteria
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Eligibility Criteria
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Select 600 Small Cell Lung Cancer Patients who are suitable for lung tissue biopsy Dosage Duration at least 45 days The usual approach group - Recruit 300 double blind random group separated SCLC patients currently used the Combined Chemotherapy on Etoposide Injection after lung tissue biopsy, like as the usual approach group. The study approach group - Recruit 300 double blind random group separated SCLC patients currently used the Combined Chemotherapy on Etoposide Capsule after lung tissue biopsy, like as the study approach group. The inclusion criteria: 1. Clinical diagnosis of Small Cell Lung Cancer (SCLC) 2. Clinical lung tissue biopsy diagnosis of SCLC 3. Suitable for enough lung tissue biopsy of SCLC 4. Random and double blind 5. Measurable disease 6. Adequate organ functions 7. Adequate performance status 8. Age 22 years old and over 9. Sign an informed consent form 10. Receive blood-drawing The exclusion criteria: 1. Pneumonectomy 2. Treatment with other anti-cancer therapies and cannot be stopped currently 3. Pregnancy 4. Breast-feeding 5. The patients with other serious intercurrent illness or infectious diseases 6. Have more than one different kind of cancer at the same time 7. Serious Allergy to Drugs 8. Serious Bleed Tendency 9. Serious Risks or Serious Adverse Events of the drug product 10. The prohibition of drug products 11. Have no therapeutic effects 12. Follow up to the most current label

Ages Eligible for Study
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Minimum Age: 22 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The usual approach group (injection + oral) The study approach group (oral)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETOPOSIDE - Usual<br>Etoposide Injection Chemotherapy Etoposide Injection Usual Approach Group | Drug: ETOPOSIDE - Usual<br>* Etoposide Injection<br>* Other names: Etoposide Injection Chemotherapy;|
| Experimental: ETOPOSIDE - Study<br>Etoposide Capsule Chemotherapy Etoposide Capsule Study Approach Group | Drug: ETOPOSIDE - Study<br>* Etoposide Capsule<br>* Other names: Etoposide Capsule Chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Find Etoposide Drug Targets' SNP Genotypes which are effectiveness-associated, and which are risk-associated. | Recruit 300 double blind random group separated SCLC patients currently used the Combined Chemotherapy on Etoposide Injection after lung tissue biopsy, like as the usual approach group. Recruit 300 double blind random group separated SCLC patients currently used the Combined Chemotherapy on Etoposide Capsule after lung tissue biopsy, like as the study approach group. Assay above every SCLC patient-specific Etoposide (VP-16) drug target (Topoisomerase II) SNP genotype in his or her SCLC cell whole genome DNA with Oxford precisely sequencing. Assay above every SCLC patient-specific Etoposide (VP-16) drug target (CYP4503A4) SNP genotype in his or her WBC cell whole genome DNA with Oxford precisely sequencing. | Duration at least 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCLC, Etoposide, SNP, Topo, CYP, Genotype, Oncology, Genetics, Lung, Cancer