Neoadjuvant Chemoradiotherapy With or Without Gefitinib in Treating Patients With Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer - Full Text View

Sponsor:	University of Alabama at Birmingham
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00062270

Purpose

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 the tumor. Combining chemotherapy and radiation therapy with gefitinib before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: Phase I/II trial to compare the effectiveness of neoadjuvant chemoradiotherapy with or without gefitinib in treating patients who are undergoing surgery for stage III non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Drug: cisplatin Drug: docetaxel Drug: gefitinib Drug: gemcitabine hydrochloride Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	Neoadjuvant Chemoradiotherapy (Gemcitabine/Cisplatin and Taxotere) With or Without Co-Administration of ZD 1839 (Iressa) for Stage IIIA (N2) and Selective Stage IIIB Non-Small Cell Lung Cancer: Phase I-II Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Gemcitabine Docetaxel Gemcitabine hydrochloride ZD1839

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

May 2003

Detailed Description:

OBJECTIVES: Phase I:

Determine the tolerability and toxicity of gefitinib in combination with chest radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer.

Phase II:

Compare the pathologic response (complete response and rate of downstaging) in patients treated with neoadjuvant chemoradiotherapy with vs without gefitinib.
Compare the feasibility and toxicity profile of these regimens in these patients.
Compare the resection rates, time to progression, and overall survival of patients treated with these regimens.
Correlate the percent decline in the fludeoxyglucose F 18 standardized uptake value as measured by position emission tomography with pathologic response at resection, time to progression, and overall survival in patients treated with these regimens.

OUTLINE:

Phase I: This is an open-label, nonrandomized study.
- Induction: Patients receive cisplatin IV over 60 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
- Consolidation: Within 3-4 weeks after the completion of induction therapy, patients undergo radiotherapy once daily 5 days a week for 5 weeks and receive oral gefitinib once daily concurrently.

A cohort of 3-6 patients receives consolidation chemoradiotherapy. If 2 of 6 patients experience dose-limiting toxicity, gefitinib is deleted from consolidation therapy in phase II arm II.

Surgery: Patients without disease progression after consolidation therapy undergo thoracotomy within 3-5 weeks after consolidation.
Maintenance: Beginning 2-4 weeks after surgery, patients receive oral gefitinib once daily for 6 months in the absence of disease progression.
- Phase II: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive induction and consolidation therapy (with the exception of gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation. Patients undergo surgery as in phase I.
Arm II: Patients receive therapy (including gefinitib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation.

Patients are followed every 6-8 weeks for the first 12 months and then every 4-6 months thereafter.

PROJECTED ACCRUAL: A total of 43-80 patients (3-6 patients for phase I and 40-74 patients [20-37 per treatment arm] for phase II) will be accrued for this study.

Eligibility

Ages Eligible for Study:	19 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed non-small cell lung cancer
- Stage IIIA (T1-3, N2)
  - Positive (pathological) ipsilateral mediastinal node
- Selective stage IIIB meeting all of the following criteria:
  - No pleural/pericardial effusion or superior vena cava syndrome
  - T4 due to invasion of carina, trachea, or mediastinal structures
  - Mediastinal N3 nodes (without supraclavicular or cervical adenopathy)
Proof of N2 or N3 status requires surgical staging of the mediastinum (mediastinoscopy, mediastinotomy, or exploration)
Expression of epidermal growth factor receptor (at least 1+) by immunohistochemistry
Measurable disease by contrast CT scan allowed
No bronchoalveolar cell carcinoma
No prior diagnosis of lung cancer

PATIENT CHARACTERISTICS:

Age

19 and over

Performance status

ECOG 0-1 (0-2 if albumin is at least 0.85 times lower limit of normal and weight loss within 3 months before diagnosis is no greater than 10%)

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 150,000/mm^3
Hemoglobin at least 10 g/dL

Hepatic

Bilirubin normal
AST and ALT no greater than 2.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 2 times ULN
- Alkaline phosphatase between 1.5-2 times ULN requires a negative bone scan for metastatic bone disease

Renal

Creatinine no greater than 1.4 mg/dL OR
Creatinine clearance at least 60 mL/min

Cardiac

No myocardial infarction within the past 3 months
No active angina
No unstable heart rhythms
No congestive heart failure

Pulmonary

Postresection predicted FEV_1% greater than 35%
- Predicted FEV_1% is defined as FEV_1% times percent perfusion to uninvolved lung from quantitative lung V/Q scan report

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 6 weeks after study treatment
No other uncontrolled medical illness
No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
No grade 2 or greater peripheral neuropathy
No concurrent ocular inflammation or infection
No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
No known severe hypersensitivity reaction to gefinitib or any of its excipients
No prior severe allergic reaction to platinum-containing compounds or mannitol

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) during chemotherapy

Chemotherapy

No prior chemotherapy for lung cancer

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy for lung cancer

Surgery

Recovered from prior major surgery
No concurrent opthalmic surgery

Other

More than 30 days since prior unapproved or investigational drugs
No concurrent use of the following drugs:
- Phenytoin
- Carbamazepine
- Barbiturates
- Rifampin
- Phenobarbital
- Hypericum perforatum (St. John's Wort)
- Warfarin
No concurrent retinoids

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00062270

Locations

United States, Alabama
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3300

Sponsors and Collaborators

University of Alabama at Birmingham

National Cancer Institute (NCI)

Investigators

Study Chair:

Francisco Robert, MD, FACP

University of Alabama at Birmingham

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00062270 History of Changes
Other Study ID Numbers:	CDR0000304674, UAB-0162, UAB-F020730006, ZENECA-ZD1839US-0207, AVENTIS-GIA-12139
Study First Received:	June 5, 2003
Last Updated:	May 30, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Docetaxel
Gefitinib
Cisplatin

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012