First-Line Combination Chemotherapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Sponsor

Yonsei University (Other)

Overall Status

Unknown status

CT.gov ID

NCT00736814

Collaborator

(none)

117

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which combination chemotherapy regimen is most effective in treating non-small cell lung cancer.

PURPOSE: This randomized phase II trial is comparing different combination chemotherapy regimens to see how well they work as first-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin Drug: docetaxel Drug: gemcitabine hydrochloride Drug: vinorelbine tartrate	Phase 2

Detailed Description

OBJECTIVES:

To assess treatment outcomes of adjuvant chemotherapy based on ERCC1 and RRM1 mRNA levels in patients with stage IIIB or IV non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

RNA is isolated from pretreatment biopsy samples and analyzed with reverse transcriptase-PCR (RT-PCR) assays to determine ERCC1 and RRM1 mRNA expression.

Arm I: Patients receive standard chemotherapy comprising docetaxel IV and carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients are treated according to ERCC1 and RRM1 mRNA expression levels as determined by RT-PCR.
Genotype A1 (high ERCC1 and high RRM1 mRNA levels): Patients receive non-platinum doublet chemotherapy comprising docetaxel and vinorelbine ditartrate IV on days 1 and 15. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Genotype A2 (high ERCC1 and low RRM1 mRNA levels): Patients receive non-platinum doublet chemotherapy comprising gemcitabine hydrochloride IV and vinorelbine ditartrate IV on days 1 and 8. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Genotype B1 (low ERCC1 and high RRM1 mRNA levels): Patients receive platinum doublet chemotherapy comprising docetaxel IV and carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Genotype B2 (low ERCC1 and low RRM1 mRNA levels): Patients receive platinum doublet chemotherapy comprising gemcitabine hydrochloride IV on days 1 and 8 and carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

117 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Genotype-driven Treatment of Advanced Non-small Cell Lung Cancer Based on mRNA Expression of ERCC1 & RRM1 as First-line Chemotherapy

Study Start Date :

Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I Patients receive standard chemotherapy of docetaxel and carboplatin.	Drug: carboplatin Given intravenously Drug: docetaxel Given intravenously
Experimental: Arm II, Genotype A1 Patients receive docetaxel and vinorelbine ditartrate.	Drug: docetaxel Given intravenously Drug: vinorelbine tartrate Given intravenously
Experimental: Arm II, Genotype A2 Patients receive gemcitabine hydrochloride and vinorelbine ditartrate.	Drug: gemcitabine hydrochloride Given intravenously Drug: vinorelbine tartrate Given intravenously
Experimental: Arm II, Genotype B1 Patients receive docetaxel and carboplatin.	Drug: carboplatin Given intravenously Drug: docetaxel Given intravenously
Experimental: Arm II, Genotype B2 Patients receive gemcitabine hydrochloride and carboplatin.	Drug: carboplatin Given intravenously Drug: gemcitabine hydrochloride Given intravenously

Outcome Measures

Primary Outcome Measures

Response rate (complete and partial responses) []

Secondary Outcome Measures

Disease control rate []
Response duration []
Progression-free survival []
Overall survival []
Toxicity []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically proven or radiologically and clinically suspected stage IIIB (with malignant pleural effusion) or IV non-small cell lung cancer
Unresectable disease
At least 1 measurable lesion (> 10 mm with spiral CT scan or > 20 mm with conventional CT scan)
No symptomatic or untreated brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy > 12 weeks
ANC ≥ 1,500/mm³
Hemoglobin > 9.0 g/dL
Platelet count ≥ 100,000/mm³
AST and ALT < 2 times upper limit of normal (ULN)
Bilirubin < 1.5 mg/dL
Creatinine < 1.5 times ULN
Not pregnant or nursing
No serious uncontrolled systemic intercurrent illness, including any of the following:
Acute myocardial infarction
Uncontrolled arrhythmia
Uncontrolled heart failure
Sepsis
Poorly controlled diabetes
No other malignancy within the last 5 years, except for carcinoma in situ of the cervix or nonmelanomatous carcinoma of the skin

PRIOR CONCURRENT THERAPY:

At least 3 weeks since prior radiotherapy, including cranial irradiation
At least 3 weeks since prior major surgery
No prior systemic chemotherapy except adjuvant chemotherapy provided it was completed more than 12 months ago