Chemotherapy With or Without Radiation Therapy Before Surgery in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer - Full Text View

Sponsor:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00030771

Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel and cisplatin, 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. Giving chemotherapy with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known if chemotherapy plus radiation therapy is more effective than chemotherapy alone before surgery in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying docetaxel and cisplatin with or without radiation therapy to see how well they work when given before surgery in treating patients with stage IIIA non-small cell lung cancer that has spread to lymph nodes in the chest.

Condition	Intervention	Phase
Lung Cancer	Biological: filgrastim Drug: cisplatin Drug: docetaxel Other: laboratory biomarker analysis Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	Preoperative Chemoradiotherapy Vs. Chemotherapy Alone In Non-Small Cell Lung Cancer (NSCLC) Patients With Mediastinal Lymph Node Metastases (Stage IIIA, N2): A Randomized Prospective Phase III Trial

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Docetaxel Filgrastim Lenograstim Granulocyte colony-stimulating factor

U.S. FDA Resources

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

Primary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]
Operability after chemotherapy [ Designated as safety issue: No ]

Secondary Outcome Measures:

Postoperative mortality assessed 30 days after surgery [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Complete resection rate after surgery [ Designated as safety issue: No ]
Objective response rate measured after completion of chemoradiotherapy [ Designated as safety issue: No ]
Incremental cost effectiveness ratio (ICER) of preoperative chemoradiotherapy versus chemotherapy alone expressed as cost per quality-adjusted life-year (QALY) or life years gained [ Designated as safety issue: No ]

Estimated Enrollment:	240
Study Start Date:	April 2001
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Compare the feasibility and efficacy of neoadjuvant chemotherapy with or without radiotherapy, in terms of event-free survival, in patients with stage IIIA non-small cell lung cancer with mediastinal lymph node metastases.

Secondary

Determine the value of positron emission tomography scans in predicting pathological response and event-free survival in patients treated with these regimens.
Assess the health economic analysis of the two regimens.
Compare the toxicity of these regimens in these patients.
Compare the objective response rate, failure pattern, and overall survival in patients treated with these regimens.
Compare the amount of serum DNA of patients before chemotherapy, before surgery, and at the second follow-up visit (i.e., 4 months after surgery or treatment failure for patients who can not be operated).
Correlate the DNA variation with tumor response, remission duration, and overall survival.
Evaluate specific serum DNA markers (e.g., beta-tubulin-, p53-, ras-mutation, DAP kinase-, CDKN2 hypermethylation present in the primary tumors) for predictivity.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to mediastinal bulk (5 cm or more vs less than 5 cm), weight loss in the past 6 months (5% or more vs less than 5%), and participating center. Patients are randomized to 1 of 2 treatment arms.

Arm A: Patients receive docetaxel IV over 1 hour followed by cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Three weeks after the last chemotherapy administration, patients undergo radiotherapy once daily 5 days a week for 3 weeks and boost radiotherapy on days 2, 5, 9, 12, 15, 17, and 19 during the same 3 weeks.
Arm B: Patients receive chemotherapy as in arm A. All patients undergo surgical resection and mediastinal lymph node dissection within 21-28 days after completion of radiotherapy (arm A) or within 21 days after completion of chemotherapy (arm B). Patients also receive filgrastim (G-CSF) during all 3 chemotherapy courses according to local guidelines. Health economic data (health insurance data) are collected from some patients to determine the incremental cost effectiveness ratio.

Some patients undergo blood collection periodically for translational research studies.

Patients are followed up at 1 month and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 240 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed non-small cell lung cancer
- Squamous, adenosquamous, large cell, or poorly differentiated
Stage IIIA (T1-3, N2, M0)
- N2 disease confirmed by 1 of the following:
  - Mediastinoscopy
  - Bronchoscopy with fine-needle aspiration or esophagoscopy
    - All N3 lymph nodes must be negative by positron-emission tomography (PET) AND CT scan (< 1 cm in the largest diameter)
  - PET scan
    - Both the primary tumor and at least 1 N2 lymph node must be positive in PET scan
    - At least 1 of the PET scan positive N2 lymph nodes is positive in the CT scan (> 1 cm in the largest diameter)
    - All N3 lymph nodes negative in PET scan

PATIENT CHARACTERISTICS:

Age:

18 to 75

Performance status:

WHO 0-1

Life expectancy:

Not specified

Hematopoietic:

WBC at least 4,000/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin normal
AST/ALT no greater than 1.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 2.5 times ULN

Renal:

Creatinine clearance greater than 60 mL/min

Cardiovascular:

Cardiac function normal
No unstable cardiac disease requiring treatment
No congestive heart failure
No angina pectoris even if medically controlled
No significant arrhythmia
No myocardial infarction in the past 3 months

Pulmonary:

Lung function appropriate

Neurologic:

No history of significant neurologic or psychiatric disorders
No psychotic disorders
No dementia
No seizures

Other:

No other prior or concurrent malignancies except nonmelanoma skin cancer, adequately treated carcinoma in situ of the cervix, or any other neoplastic disease with a disease-free interval ≥ 5 years
No active uncontrolled infection
No uncontrolled diabetes mellitus
No gastric ulcers
No pre-existing peripheral neuropathy greater than grade 1
No contraindications to corticosteroids
No other serious underlying medical condition that would preclude study participation
No socioeconomic or geographic condition that would preclude study participation
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior cytostatic chemotherapy

Endocrine therapy:

No concurrent prednisone except for treatment of acute hypersensitivity reactions or chronic low-dose treatment initiated more than 6 months prior to study entry (i.e., no greater than 20 mg methylprednisolone or equivalent)

Radiotherapy:

No prior radiotherapy to chest

Surgery:

Not specified

Other:

At least 30 days since participation in another clinical study
No other concurrent experimental drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00030771

Locations

Germany
Klinik Loewenstein gGmbH	Recruiting
Loewenstein, Germany, 74245
Contact: Contact Person 49-71-30-15-4837
Klinikum der Stadt Mannheim	Recruiting
Mannheim, Germany, D-68135
Contact: Contact Person 49-621-383-1430
Serbia
Institut za plucne bolesti	Recruiting
Sremska Kamenica, Serbia, 21204
Contact: Contact Person 381-21-480-5100
Institute of Oncology	Recruiting
Sremska Kamenica, Serbia, 21204
Contact: Contact Person 381-21-615-711
Switzerland
Kantonspital Aarau	Recruiting
Aarau, Switzerland, CH-5001
Contact: Contact Person 41-62-838-4141
Kantonsspital Baden	Recruiting
Baden, Switzerland, CH-5404
Contact: Clemens B. Caspar, MD 41-56-486-2511
	Recruiting
Baden, Switzerland, CH-5404
Contact: Antoinette Streit, MD 41-56-221-1474
Saint Claraspital AG	Recruiting
Basel, Switzerland, CH-4016
Contact: Contact Person 41-61-691-8585
Universitaetsspital-Basel	Recruiting
Basel, Switzerland, CH-4031
Contact: Contact Person 41-61-265-5075
Istituto Oncologico della Svizzera Italiana	Recruiting
Bellinzona, Switzerland, 6500
Contact: Contact Person 41-91-811-4513
Inselspital Bern	Recruiting
Bern, Switzerland, CH-3010
Contact: Contact Person 41-31-632-8169
Kantonsspital Bruderholz	Recruiting
Bruderholz, Switzerland, CH-4101
Contact: Lorenz M. Jost, MD 41-61-436-3667 lorenz.jost@ksbh.ch
Kantonsspital Graubuenden	Recruiting
Chur, Switzerland, CH-7000
Contact: Contact Person 41-81-256-6668
Kantonsspital Freiburg	Recruiting
Freiburg, Switzerland, 1708
Contact: Contact Person 41-26-436-7244
Hopital Cantonal Universitaire de Geneve	Recruiting
Geneva, Switzerland, CH-1211
Contact: Contact Person 41-22-372-7744
Centre Pluridisciplinaire d' Oncologie	Recruiting
Lausanne, Switzerland, 1011
Contact: Contact Person 41-21-314-0737
Kantonsspital Liestal	Recruiting
Liestal, Switzerland, CH-4410
Contact: Contact Person 41-61-925-2710
Kantonsspital Olten	Recruiting
Olten, Switzerland, CH-4600
Contact: Contact Person 41-62-311-4124
FMH Onkologie/Haematologie	Recruiting
Rheinfelden, Switzerland, 4310
Contact: Contact Person 41-61-836-9396
Kantonsspital - St. Gallen	Recruiting
St. Gallen, Switzerland, CH-9007
Contact: Contact Person 41-71-494-6325
Regionalspital	Recruiting
Thun, Switzerland, 3600
Contact: Contact Person 41-33-226-2639
Kantonsspital Winterthur	Recruiting
Winterthur, Switzerland, CH-8400
Contact: Contact Person 41-52-266-2552
City Hospital Triemli	Recruiting
Zurich, Switzerland, CH-8063
Contact: Contact Person 41-44-466-2747
UniversitaetsSpital Zuerich	Recruiting
Zurich, Switzerland, CH-8091
Contact: Contact Person 41-44-634-2872
Onkozentrum	Recruiting
Zurich, Switzerland, 8038
Contact: Contact Person 41-43 344-3344

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:	Miklos Pless, MD	Kantonsspital Winterthur KSW
Investigator:	Roger Stupp, MD	Centre Hospitalier Universitaire Vaudois
Investigator:	Diana Naehrig, MD	Universitaetsspital-Basel

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00030771 History of Changes
Other Study ID Numbers:	CDR0000069196, SWS-SAKK-16/00, EU-20138
Study First Received:	February 14, 2002
Last Updated:	October 6, 2010
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

squamous cell lung cancer
large cell lung cancer
stage IIIA non-small cell lung cancer
adenosquamous 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

Docetaxel
Cisplatin
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on February 12, 2012