Official Title: “A Phase III Trial Of Cisplatin/Etoposide/Radiotherapy With Consolidation Docetaxel Followed By Maintenance Therapy With ZD 1839 Or Placebo In Patients With Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer”

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells.

Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of tumors. It is not yet known whether combination chemotherapy plus radiation therapy is more effective with or without gefitinib in treating non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy plus radiation therapy with or without gefitinib in treating unresectable stage III non-small cell lung cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Active Control

Study Primary Completion Date: September 2008

OBJECTIVES: - Compare cisplatin, etoposide, radiotherapy, and docetaxel with or without gefitinib, in terms of improving overall survival and progression-free survival, in patients with unresectable stage III non-small cell lung cancer. - Determine the toxicity profile of gefitinib in these patients.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to performance status (0 vs 1), stage (stage IIIA vs IIIB), measurability of lesion (measurable vs nonmeasurable), and histologic subtype (squamous vs nonsquamous).

Patients receive induction therapy comprising cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33.

Beginning within 24 hours after starting chemotherapy, patients receive concurrent induction radiotherapy 5 days a week for 5 weeks and then boost radiotherapy 5 days a week for 1.5 weeks.

Beginning approximately 4-8 weeks after completion of chemoradiotherapy, patients with stable or responding disease receive consolidation therapy comprising docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 3 courses.

Patients with stable or responding disease are randomized to one of two treatment arms for maintenance therapy. Patients begin maintenance therapy approximately 4-7 weeks after completion of consolidation therapy. - Arm I: Patients receive oral gefitinib daily. - Arm II: Patients receive oral placebo daily. In both arms, maintenance therapy continues for a maximum of 5 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 5 years and then annually for 5 years.

PROJECTED ACCRUAL: A total of 840 patients will be accrued for this study within 3.5 years.

Intervention(s) in this Clinical Trial

• Drug: cisplatin
• Drug: docetaxel
• Drug: etoposide
• Drug: gefitinib
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed newly diagnosed single, primary bronchogenic non-small cell lung cancer (NSCLC)
• Adenocarcinoma
• Non-lobar and non-diffuse bronchoalveolar cell carcinoma
• Large cell carcinoma
• Squamous cell carcinoma
• Unresectable stage IIIA disease
• Histologically or cytologically confirmed N2 status
• Multiple and/or bulky mediastinal lymph nodes on CT scan or x-ray
• Ineligible for induction chemotherapy or chemoradiotherapy followed by surgical resection
• Ineligible for or refused participation in SWOG-9336 OR
• Stage IIIB disease
• Pathologically or radiographically documented positive N3 nodes
• No positive supraclavicular or scalene lymph nodes with disease extending up into the cervical region OR
• Any documented T4 lesions invading the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina
• Mediastinal involvement without organ involvement allowed if soft tissue mass extends directly into the mediastinum
• Radiographic criteria for involvement of main pulmonary artery allowed if mediastinal soft tissue mass is present
• Single primary parenchymal lesion
• No other lesions on same or opposite sides of the lung
• No metastatic disease involving the contralateral chest, liver, or adrenals by CT scan of upper abdomen
• No malignant pleural or pericardial effusions
• Pleural effusions visible only on CT scan or too small to tap allowed
• Measurable or evaluable disease by CT scan, MRI, x-ray, or physical exam
• No brain metastases

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Not specified

Renal:

• Creatinine clearance at least 50 mL/min

Pulmonary:

• FEV_1 at least 2.0 L OR
• FEV_1 less than 2.0 L if predicted FEV_1 of the contralateral lung is greater than 800 mL by quantitative split function testing

Other:

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other concurrent non-cancer-related illness that would preclude study therapy
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent colony-stimulating factors during induction therapy

Chemotherapy:

• See Disease Characteristics
• No prior chemotherapy for NSCLC

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy for NSCLC

Surgery:

• No prior surgical resection of NSCLC
• Prior exploratory thoracotomy, mediastinoscopy, excisional biopsy, or similar diagnostic or staging surgery allowed

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Southwest Oncology Group

Overall Clinical Trial Officials and Contacts

Karen Kelly, MD Study Chair University of Colorado at Denver and Health Sciences Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00020709

Study ID Number: CDR0000068706

ClinicalTrials.gov Identifier: NCT00020709

Health Authority: United States: Federal Government

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