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

Lung Cancer Clinical Trial

Official title:

Phase III Randomized Trial of Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients With Stage IIIA (N2) Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00113386
• Other study ID #: RTOG-0412
• Secondary ID: CDR0000429479SWO
• Status: Terminated
• Phase: Phase 3
• First received: June 7, 2005
• Last updated: June 21, 2013
• Start date: April 2005

Study information

• Verified date: June 2013
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Biological:
• filgrastim
Consolidation chemotherapy
• pegfilgrastim
Consolidation chemotherapy

Drug:
• cisplatin

• docetaxel

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Phoebe Cancer Center at Phoebe Putney Memorial Hospital	Albany	Georgia
United States	Cancer Center at Providence Alaska Medical Center	Anchorage	Alaska
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	St. Luke's Hospital Cancer Center	Bethlehem	Pennsylvania
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Memorial Hospital	Colorado Springs	Colorado
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	Cancer Care Center at John Muir Health - Concord Campus	Concord	California
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	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Frederick Memorial Hospital Regional Cancer Therapy Center	Frederick	Maryland
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Delnor Community Hospital - Geneva	Geneva	Illinois
United States	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	CCOP - Greenville	Greenville	South Carolina
United States	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	St. John's Regional Medical Center	Joplin	Missouri
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Lenoir Memorial Cancer Center	Kinston	North Carolina
United States	U.T. Cancer Institute at University of Tennessee Medical Center	Knoxville	Tennessee
United States	Moores UCSD Cancer Center	La Jolla	California
United States	Watson Clinic, LLC	Lakeland	Florida
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Dean Medical Center - Madison	Madison	Wisconsin
United States	Upper Michigan Cancer Center at Marquette General Hospital	Marquette	Michigan
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Community Cancer Center	Normal	Illinois
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
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	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	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University Cancer Institute	Portland	Oregon
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	Reid Hospital & Health Care Services, Incorporated	Richmond	Indiana
United States	Valley Hospital - Ridgewood	Ridgewood	New Jersey
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of California Davis Cancer Center	Sacramento	California
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	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St Louis	Missouri
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Madigan Army Medical Center - Tacoma	Tacoma	Washington
United States	Faxton Regional Cancer Center	Utica	New York
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (6)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, National Cancer Institute (NCI), North Central Cancer Treatment Group, Southwest Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Overall Survival		Date of death or date of last follow-up	No