Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI RTOG-0412 SWOG-S0332, RTOG-0412-SWOG-S0332, CALGB-RTOG-0412, ECOG-RTOG-0412, NCCTG-RTOG-0412, NCT00113386

Objectives

Primary

1. 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

1. Compare median and progression-free survival of patients treated with these regimens.
2. Compare clinical and pathologic response rates in patients treated with these regimens.
3. Compare the toxicity of these regimens in these patients.
4. Correlate pathological complete response with disease-free and overall survival of patients treated with these regimens.
5. 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.
6. Correlate protein profiles, using MALDI-TOF proteomic analysis of tumor and serum, with response and prognosis in patients treated with these regimens.
7. Compare quality of life of patients treated with these regimens.
8. 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.
9. Correlate comorbid conditions with survival of patients treated with these regimens.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,800/mm³
• Platelet count ≥ 100,000/mm³
• 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

• FEV₁ ≥ 2.0 L

  OR

• Predicted post-resection FEV₁ ≥ 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

Expected Enrollment

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

Outcomes

Comparison of overall survival

Comparison of progression-free survival
Comparison of median survival time
Comparison of treatment toxicity rates
Comparison of clinical and pathologic response rates
Comparison of overall survival and progression-free survival between patients with and without pathologic complete response
Association of molecular markers and overall survival, progression-free survival and response
Change in patient-reported functional status

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.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Maria Werner-Wasik, MD, Principal investigator		Ph: 215-955-7679; 800-533-3669 Email: maria.werner-wasik@mail.tju.edu

Southwest Oncology Group

Howard West, MD, Principal investigator		Ph: 206-386-2882

Cancer and Leukemia Group B

Jeffrey Crawford, MD, Protocol chair		Ph: 919-668-6688 Email: crawf006@mc.duke.edu

Eastern Cooperative Oncology Group

Chandra Belani, MD, Protocol chair(Contact information may not be current)		Ph: 412-623-3205

North Central Cancer Treatment Group

James Jett, MD, Protocol chair		Ph: 507-284-3764

Registry Information
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
Trial Start Date		2005-04-08
Registered in ClinicalTrials.gov		NCT00113386
Date Submitted to PDQ		2005-04-11
Information Last Verified		2006-12-14
NCI Grant/Contract Number		CA21661