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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


Phase 3
18 Years
N/A
Not Enrolling
Both
Lung Cancer

Thank you

Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Comparison of Overall Survival

Outcome Time Frame:

Date of death or date of last follow-up

Safety Issue:

No

Principal Investigator

Maria Werner-Wasik, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Kimmel Cancer Center (KCC)

Authority:

United States: Federal Government

Study ID:

RTOG-0412

NCT ID:

NCT00113386

Start Date:

April 2005

Completion Date:

Related Keywords:

  • Lung Cancer
  • stage IIIA non-small cell lung cancer
  • adenocarcinoma of the lung
  • large cell lung cancer
  • squamous cell lung cancer
  • bronchoalveolar cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Mayo Clinic - JacksonvilleJacksonville, Florida  32224
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
CCOP - Upstate CarolinaSpartanburg, South Carolina  29303
Medical City Dallas HospitalDallas, Texas  75230
CCOP - Atlanta RegionalAtlanta, Georgia  30342-1701
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Bronson Methodist HospitalKalamazoo, Michigan  49007
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Dean Medical Center - MadisonMadison, Wisconsin  53717
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Memorial Hospital of South BendSouth Bend, Indiana  46601
Albert Einstein Cancer CenterPhiladelphia, Pennsylvania  19141
CCOP - GreenvilleGreenville, South Carolina  29615
Siteman Cancer Center at Barnes-Jewish HospitalSaint Louis, Missouri  63110
Charles M. Barrett Cancer Center at University HospitalCincinnati, Ohio  45267-0526
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State UniversityColumbus, Ohio  43210-1240
Kimmel Cancer Center at Thomas Jefferson University - PhiladelphiaPhiladelphia, Pennsylvania  19107
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
Veterans Affairs Medical Center - PortlandPortland, Oregon  97207
CCOP - Virginia Mason Research CenterSeattle, Washington  98101
University of California Davis Cancer CenterSacramento, California  95817
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Markey Cancer Center at University of Kentucky Chandler Medical CenterLexington, Kentucky  40536-0084
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
St. John's Regional Health CenterSpringfield, Missouri  65804
St. Luke's Hospital Cancer CenterBethlehem, Pennsylvania  18015
Advocate Christ Medical CenterOak Lawn, Illinois  60453
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Hematology Oncology Associates of the Quad CitiesBettendorf, Iowa  52722
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Lenoir Memorial Cancer CenterKinston, North Carolina  28503-1678
Madigan Army Medical Center - TacomaTacoma, Washington  98431
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Memorial HospitalColorado Springs, Colorado  80909
Poudre Valley HospitalFort Collins, Colorado  80524
Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiter, Florida  33458
Community Cancer CenterNormal, Illinois  61761
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
OSF St. Francis Medical CenterPeoria, Illinois  61637
Reid Hospital & Health Care Services, IncorporatedRichmond, Indiana  47374
Genesis Regional Cancer Center at Genesis Medical CenterDavenport, Iowa  52803
Upper Michigan Cancer Center at Marquette General HospitalMarquette, Michigan  49855
Lancaster General HospitalLancaster, Pennsylvania  17604-3555
Northeast Georgia Medical CenterGainesville, Georgia  30501
Allegheny Cancer Center at Allegheny General HospitalPittsburgh, Pennsylvania  15212
Leo W. Jenkins Cancer Center at ECU Medical SchoolGreenville, North Carolina  27834
York Cancer Center at Apple Hill Medical CenterYork, Pennsylvania  17405
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical CenterGreen Bay, Wisconsin  54311
Vince Lombardi Cancer Clinic - SheboyganSheboygan, Wisconsin  53081
Methodist Cancer Center at Methodist Hospital - OmahaOmaha, Nebraska  68114
FirstHealth Moore Regional Community Hospital Comprehensive Cancer CenterPinehurst, North Carolina  28374
Oregon Health & Science University Cancer InstitutePortland, Oregon  97239-3098
Phoebe Cancer Center at Phoebe Putney Memorial HospitalAlbany, Georgia  31702
Good Samaritan Cancer Center at Good Samaritan HospitalKearney, Nebraska  68848-1990
Cancer Institute at St. John's HospitalSpringfield, Illinois  62701
Frederick Memorial Hospital Regional Cancer Therapy CenterFrederick, Maryland  21701
St. John's Regional Medical CenterJoplin, Missouri  64804
U.T. Cancer Institute at University of Tennessee Medical CenterKnoxville, Tennessee  37920-2911
Valley Hospital - RidgewoodRidgewood, New Jersey  07450
Faxton Regional Cancer CenterUtica, New York  13502
Watson Clinic, LLCLakeland, Florida  33804-5000
Cancer Care Center at John Muir Health - Concord CampusConcord, California  94524-4110
Cancer Center at Providence Alaska Medical CenterAnchorage, Alaska  99519-6604
Delnor Community Hospital - GenevaGeneva, Illinois  60134
St. Agnes Hospital Cancer CenterBaltimore, Maryland  21229