Individualized Chemotherapy Based on BRCA1 and RRM1 mRNA for Advanced Non-small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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Gemcitabine, docetaxel, CPT-11 and cisplatin are effective in 1st line treatment of advanced non-small cell lung cancer (NSCLC). Platinum-based doublets including gemcitabine, docetaxel or CPT-11 are standard 1st regimens. BRCA1 and RRM1 expression levels are reported to be associated with sensitivity of the tumor cells to cytotoxic agents. Some Phase II or III trials did prove feasibility of customized chemotherapy based upon expression levels of one or two biomarkers in the NSCLC patients. The investigators think customized chemotherapy may further improve efficacy of chemotherapy in advanced NSCLC. But there is no randomised trial to compare efficacy of standard chemotherapy with individualized chemotherapy in this setting. So, the investigators plan to initiate this phase II trial to compare efficacy between standard chemotherapy of gemcitabine/cisplatin versus customized chemotherapy in chemonaive NSCLC patients.

Detailed Description
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Primary end point:ORR Secondary end point:PFS,OS,safety,QOL,etc.

Official Title
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Individualized 1st Line Chemotherapy Based on BRCA1 and RRM1 mRNA Expression Levels for Advanced Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Gemcitabine, Docetaxel, CPT-11,Cisplatin
* Drug: gemcitabine/cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent, Histologically confirmed stage M1a or M1b NSCLC, Aged over 18 years old, Measurable disease, Life expectancy of at least 12 weeks, No prior chemotherapy or target therapy, No brain metastases or spinal cord compression, Less than 10% body weight loss, ECOG performance status 0-2, Adequate vital organ function (haematological, renal, hepatic, etc). Enough tissue for detection of BRCA1 and RRM1 expression. Exclusion Criteria: Prior systemic cytotoxic chemotherapy or EGFR TKI therapy, Positive pregnancy test, Another active malignancy, other than superficial basal cell and squamous cell or carcinoma in situ of the cervix, within the last 5 years, Patients with brain metastases or spinal cord compression, Allergy to gemcitabine, cisplatin, docetaxel, CPT-11, Any unstable systemic disease including active infection, No enough tissue for detection of BRCA1 and RRM1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Arm 1<br>Based on expression levels of RRM1 and BRCA1 mRNA，one of the four regimens will be given to each patient: Gemcitabine/cisplatin, Docetaxel/gemcitabine, CPT-11/Cisplatin, docetaxel monotherapy. The chemotherapy will be repeated every 3 week. Dose reduction or interruption for toxicity could take place at any time. | Drug: Gemcitabine, Docetaxel, CPT-11,Cisplatin<br>* Based on expression levels of RRM1 and BRCA1 mRNA，one of the four regimens will be given to each patient: Gemcitabine/cisplatin, Docetaxel/gemcitabine, CPT-11/Cisplatin, docetaxel monotherapy. The chemotherapy will be repeated every 3 week. Dose reduction or interruption for toxicity could take place at any time.<br>* Other names: CPT-11:Irinotecan;|
| Active Comparator: Arm 2<br>gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity. | Drug: gemcitabine/cisplatin<br>* gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity.<br>* Other names: gemcitabine:Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | to evaluate ORR during 6-8 weeks after all cycles complete | tumor assessment 6-8 weeks after the initiation of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | PFS is evaluated in the 24th month since the treatment began | 24 months | 
| duration of response | evaluated in the 24th month since the treatment began | 24 months | 
| overall survival | evaluated in the 24th month since the treatment began | 24 months | 
| safety | evaluated in the 24th month since the treatment began | 24 months | 
| Quality Of Life | evaluated in the 24th month since the treatment began | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy, Individual therapy, RRM1, BRCA1