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

Tongji University

Status and phase: Unknown; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: gemcitabine/cisplatin; Drug: Gemcitabine, Docetaxel, CPT-11,Cisplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT01424709

BRAVO study

Details and patient eligibility

About

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.

Full description

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

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Arm 1

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine, Docetaxel, CPT-11,Cisplatin

Arm 2

Active Comparator group

Description:

gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity.

Treatment:

Drug: gemcitabine/cisplatin