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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00736814
• Other study ID #: CDR0000609880
• Secondary ID: YONSEI-4-2008-01
• Status: Recruiting
• Phase: Phase 2
• First received: August 15, 2008
• Last updated: February 23, 2011
• Start date: June 2008

Study information

• Verified date: August 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 117
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• carboplatin
Given intravenously
• docetaxel
Given intravenously
• gemcitabine hydrochloride
Given intravenously
• vinorelbine tartrate
Given intravenously

Locations

Country	Name	City	State
Korea, Republic of	Yonsei Cancer Center at Yonsei University Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (complete and partial responses)			No
Secondary	Disease control rate			No
Secondary	Response duration			No
Secondary	Progression-free survival			No
Secondary	Overall survival			No
Secondary	Toxicity			Yes