Vinorelbine, Gemcitabine, and Docetaxel Compared With Paclitaxel and Carboplatin in Treating Patients With Advanced Non-Small Cell Lung Cancer

Phase III Randomized Comparison Study of Vinorelbine, Gemcitabine, and Docetaxel Versus Paclitaxel and Carboplatin in Patients With Advanced Non-Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy, such as vinorelbine, gemcitabine, docetaxel, paclitaxel, and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying how well giving vinorelbine together with gemcitabine and docetaxel works compared to giving paclitaxel together with carboplatin in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: docetaxel; Drug: gemcitabine hydrochloride; Drug: paclitaxel; Drug: vinorelbine tartrate

Detailed Description

OBJECTIVES:

Primary

• Compare the therapeutic effect of vinorelbine, gemcitabine, and docetaxel vs paclitaxel and carboplatin in patients with advanced non-small cell lung cancer.
• Compare the overall survival of patients treated with these regimens.

Secondary

• Compare the response rate in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive vinorelbine IV and gemcitabine IV on days 1 and 8. Treatment repeats every 21 days for 3 courses. Patients then receive docetaxel IV on day 1. Treatment repeats every 21 days for 3 courses.
• Arm II: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 21 days for 6 courses.

Patients are followed for 1 year.

PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 2 years.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 466-8560
    • Nagoya University Hospital
  • Asahikawa, Japan, 078 8510
    • Asahikawa Medical College
  • Chiba-ken, Japan, 277-8577
    • National Cancer Center Hospital East
  • Ehime, Japan, 791-0281
    • National Hospital Organization - Ehime National Hospital
  • Fukuoka, Japan, 820-0018
    • Aso Iizuka Hospital
  • Hiroshima, Japan, 737-0023
    • National Hospital Organization - Medical Center of Kure
  • Hokkaido, Japan, 070-0901
    • National Hospital Organization - Dohoku National Hospital
  • Kanagawa, Japan, 251-8550
    • Fujisawa City Hospital
  • Kochi-shi, Japan, 780-8065
    • National Hospital Organization - Kochi Hospital
  • Kyoto, Japan, 615-8256
    • Kyoto-Katsura Hospital
  • Ogaki-shi, Japan, 503-8502
    • Ogaki Municipal Hospital
  • Okayama, Japan, 701-1192
    • National Hospital Organization - Okayama Medical Center
  • Okinawa, Japan, 901-2214
    • National Hospital Organization - Okinawa Hospital
  • Osaka, Japan, 530-0012
    • Osaka Saiseikai Nakatsu Hospital
  • Osaka, Japan, 591-8555
    • National Hospital Organization - Osaka National Hospital
  • Osaka, Japan, 569-1096
    • Takatsuki Red Cross Hospital
  • Osaka-shi, Japan, 558-0056
    • Osaka General Medical Center
  • Saitama, Japan, 362-0803
    • Saitama Cancer Center
  • Takamatsu, Japan, 760-8571
    • Takamatsu Red Cross Hospital
  • Tokyo, Japan, 113-8519
    • Tokyo Medical and Dental University
  • Tokyo, Japan, 160
    • Tokyo Medical University
  • Tottori, Japan, 683-8504
    • Tottori University Hospital
  • Toyama, Japan, 933-8555
    • Koseiren Takaoka Hospital
  • Toyama, Japan, 930-0194
    • Toyama Medical and Pharmaceutical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC) meeting criteria for 1 of the following:

  • Newly diagnosed selected stage IIIB (T4 lesion due to malignant pleural effusion) disease
  • Newly diagnosed stage IV disease
  • Recurrent disease after prior surgery and/or radiotherapy

• The following cellular subtypes are allowed:

  • Adenocarcinoma
  • Large cell carcinoma
  • Squamous cell carcinoma
  • Unspecified carcinoma

• Measurable or nonmeasurable disease by CT scan, MRI, x-ray, physical examination, or bone scintigraphy

  • Pleural effusions, ascites, and laboratory parameters are not allowed as the only evidence of disease
  • Disease must be present outside area of prior surgical resection
  • Disease must be present outside area of prior radiotherapy OR new lesion documented
• No known brain metastases by CT scan or MRI within the past 6 weeks
• No pleural or pericardial effusions requiring treatment

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• SGOT or SGPT ≤ 2 times ULN
• Alkaline phosphatase ≤ 2 times ULN

Renal

• Creatinine ≤ ULN
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No myocardial infarction within the past year
• No ventricular arrhythmia requiring medical intervention

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No prior allergic drug reaction attributed to Cremophor or polysorbate 80
• No disorder associated with lung cancer with life-threatening consequences
• No motor or sensory neuropathy ≥ grade 2
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
• No uncontrolled diabetes

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy for NSCLC

Chemotherapy

• No prior systemic chemotherapy for NSCLC

Endocrine therapy

• No prior or concurrent steroid-type hormonal therapy (e.g., ethinyl estradiol)

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• At least 2 weeks since prior thoracic or other major surgery and recovered

Other

• No prior or concurrent azole antifungal therapy (e.g., ketoconazole, miconazole, or itraconazole)
• No prior or concurrent macrolides (e.g., erythromycin or clarithromycin)
• No prior or concurrent cyclosporine, terfenadine, benzodiazepines (e.g., diazepam, triazolam, or midazolam), or retinoids
• No prior or concurrent calcium antagonists (e.g., diltiazem, nifedipine, or verapamil)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Japan Multinational Trial Organization
• Investigators: Study Chair: Masaaki Kawahara, MD, National Hospital Organization Osaka National Hospital

Publications and helpful links

General Publications

• Teramukai S, Kitano T, Kishida Y, Kawahara M, Kubota K, Komuta K, Minato K, Mio T, Fujita Y, Yonei T, Nakano K, Tsuboi M, Shibata K, Furuse K, Fukushima M. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009 Jul;45(11):1950-8. doi: 10.1016/j.ejca.2009.01.023. Epub 2009 Feb 21.
• Kubota K, Kawahara M, Ogawara M, Nishiwaki Y, Komuta K, Minato K, Fujita Y, Teramukai S, Fukushima M, Furuse K; Japan Multi-National Trial Organisation. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol. 2008 Dec;9(12):1135-42. doi: 10.1016/S1470-2045(08)70261-4. Epub 2008 Nov 13.
• Teramukai S, Nishimura T, Nakagawa M, et al.: Predictors and impacts of second-line chemotherapy on survival after progression in patients with advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 25 (Suppl 18): A-7675, 2007.

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 9, 2004
• First Posted (Estimate): March 10, 2004

Study Record Updates

• Last Update Posted (Estimate): September 17, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: April 1, 2005

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Docetaxel; Carboplatin; Paclitaxel; Vinorelbine
• Other Study ID Numbers: CDR0000355138; JMTO-LC00-03