Clinical trial NCT00113386: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
adenocarcinoma of the lung
large cell lung cancer
squamous cell lung cancer
bronchoalveolar cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: SWOG Cancer Research Network
name: Cancer and Leukemia Group B
name: Eastern Cooperative Oncology Group
name: North Central Cancer Treatment Group
First posted: 2005-06-08
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Comparison of Overall Survival
timeFrame: Date of death or date of last follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Cancer Center at Providence Alaska Medical Center
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Concord
country: United States
facility: Cancer Care Center at John Muir Health - Concord Campus
state: California
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Colorado Springs
country: United States
facility: Memorial Hospital
state: Colorado
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic, LLC
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Albany
country: United States
facility: Phoebe Cancer Center at Phoebe Putney Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Geneva
country: United States
facility: Delnor Community Hospital - Geneva
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
state: Illinois
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services, Incorporated
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Davenport
country: United States
facility: Genesis Regional Cancer Center at Genesis Medical Center
state: Iowa
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Frederick
country: United States
facility: Frederick Memorial Hospital Regional Cancer Therapy Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Marquette
country: United States
facility: Upper Michigan Cancer Center at Marquette General Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Joplin
country: United States
facility: St. John's Regional Medical Center
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Kearney
country: United States
facility: Good Samaritan Cancer Center at Good Samaritan Hospital
state: Nebraska
city: Omaha
country: United States
facility: Methodist Cancer Center at Methodist Hospital - Omaha
state: Nebraska
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Ridgewood
country: United States
facility: Valley Hospital - Ridgewood
state: New Jersey
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Utica
country: United States
facility: Faxton Regional Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center at ECU Medical School
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Cancer Center
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Portland
country: United States
facility: Veterans Affairs Medical Center - Portland
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University Cancer Institute
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center at Apple Hill Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Knoxville
country: United States
facility: U.T. Cancer Institute at University of Tennessee Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center - Tacoma
state: Washington
city: Green Bay
country: United States
facility: Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center
state: Wisconsin
city: Madison
country: United States
facility: Dean Medical Center - Madison
state: Wisconsin
city: Sheboygan
country: United States
facility: Vince Lombardi Cancer Clinic - Sheboygan
state: Wisconsin
Study officials:
affiliation: Sidney Kimmel Cancer Center at Thomas Jefferson University
name: Maria Werner-Wasik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
name: Howard L. West, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Cancer Institute
name: Jeffrey Crawford, MD
role: STUDY_CHAIR
affiliation: University of Pittsburgh
name: Chandra P. Belani, MD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: James R. Jett, MD
role: STUDY_CHAIR
References: