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

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

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.

Study Overview

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

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200433
    • Medical Department, Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 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; 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.; Other Names: gemcitabine:Gemzar; Docetaxel:Taxotere; CPT-11:Irinotecan
Active Comparator: Arm 2; gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity.	Drug: gemcitabine/cisplatin; gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity.; Other Names: gemcitabine:Gemzar

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tongji University
• Investigators: Principal Investigator: Caicun Zhou, Ph.D, Tongji University Affiliated Shanghai Pulmonary Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: May 9, 2011
• First Submitted That Met QC Criteria: August 26, 2011
• First Posted (Estimate): August 29, 2011

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 23, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Chemotherapy; BRCA1; Individual therapy; RRM1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Gemcitabine; Docetaxel; Cisplatin; Irinotecan
• Other Study ID Numbers: BRAVO study