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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated 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 :	June 2008

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Primary Outcome Measures :

1. Response rate (complete and partial responses)

Secondary Outcome Measures :

1. Disease control rate
2. Response duration
3. Progression-free survival
4. Overall survival
5. Toxicity

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

Korea, Republic of
Yonsei Cancer Center at Yonsei University Medical Center	Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Byung Chul Cho 82-2-222-822

Sponsors and Collaborators

Yonsei University

Investigators

Principal Investigator:	Byung Chul Cho	Yonsei University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

ClinicalTrials.gov Identifier:	NCT00736814 History of Changes
Other Study ID Numbers:	CDR0000609880; YONSEI-4-2008-0132; SANOFI-AVENTIS-YONSEI-4-2008-0
First Posted:	August 18, 2008
Last Update Posted:	February 24, 2011
Last Verified:	August 2009

Keywords provided by National Cancer Institute (NCI):

stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gemcitabine; Docetaxel; Vinorelbine; Carboplatin	Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic