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

Phase 2

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Gemcitabine, Docetaxel, CPT-11,Cisplatin; Drug: gemcitabine/cisplatin

• Registration Number: NCT01424709
• Lead Sponsor: Tongji University

Brief Summary

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

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

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2011-05-09
• Study First Submitted QC: 2011-08-26
• Study First Posted: 2011-08-29
• Primary Completion: 2014-05
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-23
• Last Update Posted: 2014-09-25
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Written informed consent,
2. Histologically confirmed stage M1a or M1b NSCLC,
3. Aged over 18 years old,
4. Measurable disease,
5. Life expectancy of at least 12 weeks,
6. No prior chemotherapy or target therapy,
7. No brain metastases or spinal cord compression,
8. Less than 10% body weight loss,
9. ECOG performance status 0-2,
10. Adequate vital organ function (haematological, renal, hepatic, etc).
11. Enough tissue for detection of BRCA1 and RRM1 expression.

Exclusion Criteria

1. Prior systemic cytotoxic chemotherapy or EGFR TKI therapy,
2. Positive pregnancy test,
3. Another active malignancy, other than superficial basal cell and squamous cell or carcinoma in situ of the cervix, within the last 5 years,
4. Patients with brain metastases or spinal cord compression,
5. Allergy to gemcitabine, cisplatin, docetaxel, CPT-11,
6. Any unstable systemic disease including active infection,
7. No enough tissue for detection of BRCA1 and RRM1

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	Gemcitabine, Docetaxel, CPT-11,Cisplatin	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.
Arm 2	gemcitabine/cisplatin	gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall response rate	tumor assessment 6-8 weeks after the initiation of chemotherapy	to evaluate ORR during 6-8 weeks after all cycles complete

Secondary Outcome Measures

Name	Time	Method
Progression free survival	24 months	PFS is evaluated in the 24th month since the treatment began
duration of response	24 months	evaluated in the 24th month since the treatment began
overall survival	24 months	evaluated in the 24th month since the treatment began
safety	24 months	evaluated in the 24th month since the treatment began
Quality Of Life	24 months	evaluated in the 24th month since the treatment began

Trial Locations

Locations (1)

Medical Department, Shanghai Pulmonary Hospital; 🇨🇳 Shanghai, China