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

Condition(s) targeted: Lung Cancer

Intervention: carboplatin (Drug); docetaxel (Drug); gemcitabine hydrochloride (Drug); vinorelbine ditartrate (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Yonsei University

Official(s) and/or principal investigator(s):
Byung Chul Cho, Principal Investigator, Affiliation: Yonsei University

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.

Official title: Genotype-Driven Treatment of Advanced Non-Small Cell Lung Cancer Based on mRNA Expression of ERCC1 & RRM1 as First-Line Chemotherapy

Study design: Treatment, Randomized, Open Label, Active Control

Primary outcome: Response rate (complete and partial responses)

Secondary outcome:

Disease control rate

Response duration

Progression-free survival

Overall survival

Toxicity

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Yonsei Cancer Center at Yonsei University Medical Center, Seoul 120-752, Korea, Republic of; Recruiting
Byung Chul Cho, Phone: 82-2-2228-2262

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2008
Last updated: August 15, 2008