Cisplatin and Docetaxel With or Without Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Newly Diagnosed Stage III Non-Small Cell Lung Cancer

NCT ID: NCT00113386

Last Updated: 2013-06-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin and docetaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) together with radiation therapy before surgery may shrink the tumor so it can be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving cisplatin and docetaxel together with radiation therapy is more effective than giving cisplatin together with docetaxel in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying cisplatin, docetaxel, and radiation therapy to see how well they work compared to cisplatin and docetaxel in treating patients who are undergoing surgery for newly diagnosed stage III non-small cell lung cancer.

Detailed Description

OBJECTIVES:

Primary

• Compare overall survival of patients with newly diagnosed favorable prognosis stage IIIA non-small cell lung cancer treated with neoadjuvant cisplatin and docetaxel with vs without thoracic conformal radiotherapy followed by surgical resection and docetaxel.

Secondary

• Compare median and progression-free survival of patients treated with these regimens.
• Compare clinical and pathologic response rates in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Correlate pathological complete response with disease-free and overall survival of patients treated with these regimens.
• Correlate DNA damage repair genes (ERCC1 and XRCC1), microtubule-related proteins (TUBB-III and MAP4), and shed tumor DNA with response and outcome in patients treated with these regimens.
• Correlate protein profiles, using MALDI-TOF proteomic analysis of tumor and serum, with response and prognosis in patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.
• Determine the efficacy of fludeoxyglucose F 18 positron emission tomography scanning in assessing pathological response of the tumor and the mediastinal lymph nodes and in predicting long-term outcome in patients treated with these regimens.
• Correlate comorbid conditions with survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T stage (T1 vs T2-3), number of involved mediastinal lymph nodes (1 vs 2 or more vs not evaluable), and nodal micrometastases vs clinically involved nodes (mN2 vs cN2).

• Induction therapy: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV over 1 hour and docetaxel IV over 1 hour on days 1 and 22.
• Arm II: Patients undergo thoracic conformal radiotherapy once daily 5 days a week for approximately 5½ weeks (total of 28 doses). Patients also receive cisplatin IV over 1 hour on days 1, 8, 22, and 29 and docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29.
• Surgery: Within 4-8 weeks after completion of induction therapy, patients with stable disease or better undergo a lobectomy or pneumonectomy with a formal systematic mediastinal lymph node dissection.
• Consolidation therapy: Beginning 4-6 weeks after surgery, patients receive docetaxel IV over 1 hour on days 1, 22, and 43 and pegfilgrastim or filgrastim (G-CSF) subcutaneously on days 2, 23, and 44.

Quality of life is assessed at baseline, within 2 weeks after completion of induction therapy, and then at 6 and 12 months after surgery.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 574 patients will be accrued for this study within 4 years.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction chemotherapy, surgery, consolidation chemotherapy

Induction/surgery/consolidation

Group Type: OTHER

filgrastim

Intervention Type: BIOLOGICAL

Consolidation chemotherapy

pegfilgrastim

Intervention Type: BIOLOGICAL

Consolidation chemotherapy

cisplatin

Intervention Type: DRUG

docetaxel

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

Chemotherapy and radiation, surgery, consolidation ch

Induction/radiation/surgery/cosolidation

Group Type: OTHER

filgrastim

Intervention Type: BIOLOGICAL

Consolidation chemotherapy

pegfilgrastim

Intervention Type: BIOLOGICAL

Consolidation chemotherapy

cisplatin

Intervention Type: DRUG

docetaxel

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Interventions

filgrastim

Consolidation chemotherapy

Intervention Type: BIOLOGICAL

pegfilgrastim

Consolidation chemotherapy

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

docetaxel

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC)*, including any of the following cellular types:

• Adenocarcinoma
• Squamous cell carcinoma
• Large cell carcinoma
• Non-lobar and non-diffuse bronchoalveolar cell carcinoma
• NSCLC not otherwise specified NOTE: *Diagnosed within the past 3 months; diagnosis by mediastinal nodal biopsy or needle aspiration allowed provided a distinct lung primary (separate from the nodes) is clearly evident on CT scan
• Stage IIIA disease

• T1-T3 disease

• If pleural effusion is present, must meet ≥ 1 of the following criteria to exclude T4 disease:

• Pleural effusion cytologically negative by thoracentesis
• Documented absence of pleural metastases and pleural effusion cytologically negative by thoracoscopy (for patients with pleural effusion on CT scan [but not on chest x-ray] that is deemed too small to tap safely under either CT scan or ultrasound guidance)
• Confirmed positive ipsilateral mediastinal lymph node(s) (N2 disease)**, with or without positive ipsilateral hilar nodes, by mediastinoscopy, mediastinotomy, endoscopic ultrasound-guided transesophageal biopsy, thoracotomy, video-assisted thoracoscopy, Wang needles, or fine needle aspiration under bronchoscopic or CT guidance

• N2 nodes must be separate from primary tumor by CT scan or surgical exploration AND maximum diameter ≤ 3.0 cm
• Mediastinoscopy OR other means of mediastinal lymph node biopsy required (regardless of the primary tumor site) for patients with subcarinal lymphadenopathy by size criteria or by positron emission tomography (PET) scan
• If the lymph nodes in the contralateral mediastinum and neck are visible by contrast CT scan of the chest AND are ≥ 1.0 cm OR if contralateral involvement is suggested by PET scan, lymph nodes must be confirmed negative by one of the above diagnostic procedures AND N3 status must be confirmed negative by histology or cytology
• No palpable lymph nodes in the supraclavicular areas or higher in the neck unless proven benign by excisional biopsy
• A nodal biopsy or needle aspiration may be omitted provided all of the following criteria are true:

• Paralyzed left true vocal cord by bronchoscopy or indirect laryngoscopy
• Nodes visible in the aortopulmonary window (level 5) region on CT scan
• Distinct primary tumor (separate from the nodes) is visible by CT scan
• No evidence of subcarinal nodal involvement by CT scan NOTE: **PET scan positivity is not sufficient to establish N2 nodal status
• Measurable disease by chest x-ray and/or contrast-enhanced CT scan
• Candidate for surgery

• Resectable disease
• No distant metastases, including other ipsilateral or contralateral parenchymal lesions or liver or adrenal metastases, by history or physical examination, fludeoxyglucose F 18 PET scan, MRI or CT scan of the brain, chest x-ray and/or CT scan of the lungs and upper abdomen

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,800/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)

Hepatic

• ALT and AST ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• No hepatic insufficiency resulting in clinical jaundice or coagulation defects

Renal

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No unstable angina or congestive heart failure requiring hospitalization within the past 6 months
• No transmural myocardial infarction within the past 6 months

Pulmonary

• FEV_1 ≥ 2.0 L OR
• Predicted post-resection FEV_1 ≥ 0.8 L
• DLCO ≥ 50% of predicted
• No chronic obstructive pulmonary disease exacerbation
• No other respiratory illness requiring hospitalization or that would preclude study therapy

Immunologic

• No AIDS
• No prior allergic reaction to the study drugs
• No history of severe hypersensitivity to other drugs formulated with polysorbate 80
• No acute bacterial or fungal infection requiring IV antibiotics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No unintentional weight loss > 5% of body weight within the past 6 months
• No pre-existing peripheral neuropathy ≥ grade 2
• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
• No other severe active comorbidity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biological agent for this cancer
• No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim during study induction therapy (for patients randomized to the chemoradiotherapy arm)

Chemotherapy

• No prior systemic chemotherapy for this cancer

• Prior chemotherapy for a different cancer allowed

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields
• No routine post-operative radiotherapy
• No concurrent intensity modulated radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior gefitinib for this cancer
• No concurrent amifostine

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria Werner-Wasik, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Cancer Center at Thomas Jefferson University

Howard L. West, MD

Role: PRINCIPAL_INVESTIGATOR

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Jeffrey Crawford, MD

Role: STUDY_CHAIR

Duke Cancer Institute

Chandra P. Belani, MD

Role: STUDY_CHAIR

University of Pittsburgh

James R. Jett, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Cancer Center at Providence Alaska Medical Center

Anchorage, Alaska, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, United States

Moores UCSD Cancer Center

La Jolla, California, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

University of California Davis Cancer Center

Sacramento, California, United States

Memorial Hospital

Colorado Springs, Colorado, United States

Front Range Cancer Specialists

Fort Collins, Colorado, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Ella Milbank Foshay Cancer Center at Jupiter Medical Center

Jupiter, Florida, United States

Watson Clinic, LLC

Lakeland, Florida, United States

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Phoebe Cancer Center at Phoebe Putney Memorial Hospital

Albany, Georgia, United States

CCOP - Atlanta Regional

Atlanta, Georgia, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Delnor Community Hospital - Geneva

Geneva, Illinois, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Community Cancer Center

Normal, Illinois, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, United States

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, United States

OSF St. Francis Medical Center

Peoria, Illinois, United States

Cancer Institute at St. John's Hospital

Springfield, Illinois, United States

Reid Hospital & Health Care Services, Incorporated

Richmond, Indiana, United States

Memorial Hospital of South Bend

South Bend, Indiana, United States

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, United States

Genesis Regional Cancer Center at Genesis Medical Center

Davenport, Iowa, United States

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Frederick Memorial Hospital Regional Cancer Therapy Center

Frederick, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Upper Michigan Cancer Center at Marquette General Hospital

Marquette, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

St. John's Regional Medical Center

Joplin, Missouri, United States

St. John's Regional Health Center

Springfield, Missouri, United States

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, United States

Methodist Cancer Center at Methodist Hospital - Omaha

Omaha, Nebraska, United States

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Valley Hospital - Ridgewood

Ridgewood, New Jersey, United States

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Faxton Regional Cancer Center

Utica, New York, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Leo W. Jenkins Cancer Center at ECU Medical School

Greenville, North Carolina, United States

Lenoir Memorial Cancer Center

Kinston, North Carolina, United States

FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center

Pinehurst, North Carolina, United States

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

Columbus, Ohio, United States

Veterans Affairs Medical Center - Portland

Portland, Oregon, United States

Oregon Health & Science University Cancer Institute

Portland, Oregon, United States

St. Luke's Hospital Cancer Center

Bethlehem, Pennsylvania, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Lancaster General Hospital

Lancaster, Pennsylvania, United States

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, United States

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

York Cancer Center at Apple Hill Medical Center

York, Pennsylvania, United States

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

CCOP - Greenville

Greenville, South Carolina, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

U.T. Cancer Institute at University of Tennessee Medical Center

Knoxville, Tennessee, United States

Medical City Dallas Hospital

Dallas, Texas, United States

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Madigan Army Medical Center - Tacoma

Tacoma, Washington, United States

Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center

Green Bay, Wisconsin, United States

Dean Medical Center - Madison

Madison, Wisconsin, United States

Vince Lombardi Cancer Clinic - Sheboygan

Sheboygan, Wisconsin, United States

Countries

United States

Other Identifiers

CDR0000429479

Identifier Type: -

Identifier Source: secondary_id

SWOG-S0332

Identifier Type: -

Identifier Source: secondary_id

CALGB-RTOG-0412

Identifier Type: -

Identifier Source: secondary_id

ECOG-RTOG-0412

Identifier Type: -

Identifier Source: secondary_id

NCCTG-RTOG-0412

Identifier Type: -

Identifier Source: secondary_id

RTOG-0412

Identifier Type: -

Identifier Source: org_study_id