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

Alternate Title

High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Basic Trial Information

Special Category: CTSU trial

Objectives

Primary

1. To compare the overall survival of patients with newly diagnosed, unresectable stage IIIA or IIIB non-small cell lung cancer treated with high- versus standard-dose conformal radiotherapy with concurrent and consolidation chemotherapy comprising carboplatin and paclitaxel.
2. To compare the overall survival of patients treated with versus without cetuximab in the setting of concurrent chemotherapy

Secondary

1. To compare progression-free survival and local-regional tumor control in patients treated with these regimens.
2. To compare the toxicity of high- versus standard-dose conformal radiotherapy and concurrent chemotherapy with versus without cetuximab in these patients.
3. To investigate the prognostic and predictive effects of gross tumor volume on overall survival of patients treated with these regimens.
4. To compare the quality of life of patients treated with these regimens.
5. To correlate outcomes (i.e., survival, toxicity, or QOL) in these patients with biological parameters.
6. To analyze the predictive value of pre-treatment standardized uptake value (SUV) of PET scan in predicting survival, distant metastasis, and local-regional control in patients treated with these regimens.
7. To explore biological markers to predict clinical outcome including survival, distant metastasis, local-regional control, and QOL (including toxicity) in patients treated with these regimens.
8. To prospectively collect and bank tissue, blood, and urine specimens for future biomarker analyses in predicting clinical outcome in patients treated with these regimens.
9. To investigate associations between EGFR expression and toxicity, response, overall survival, and progression-free survival.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed newly diagnosed non-small cell lung cancer (NSCLC)
  • Stage IIIA or IIIB disease
    • N3 supraclavicular disease or contralateral hilar lymph node involvement (i.e. greater than 1.5 cm on short axis or positive on PET scan) not allowed
    • N2 or N3 disease and an undetectable NSCLC primary tumor allowed
  • Unresectable or inoperable disease

• No distant metastases

• Pleural effusion allowed provided effusion is minimal and none of the following conditions are present:
  • Cytologically positive pleural effusion detectable by CT scan and chest x-ray (pleuracentesis required to confirm negative cytology of pleural fluid)
  • Greater than minimal pleural effusions (minimal effusions not detectable by chest x-ray and too small to tap safely are allowed)
  • Exudative pleural effusions, regardless of cytology
  • Malignant pleural effusion (T4 incurable disease)

• Measurable or evaluable disease

Prior/Concurrent Therapy:

• At least 3 weeks since prior exploratory thoracotomy (if performed)
• Prior systemic chemotherapy allowed, provided it was not given for NSCLC
• No prior therapy that specifically and directly targets the EGFR pathway
• No prior radiotherapy to the region of NSCLC that would result in overlap of radiotherapy fields
• No concurrent WBC growth factors (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF]) given during radiotherapy or prophylactically during consolidation chemotherapy

Patient Characteristics:

• Zubrod performance status 0-1
• ANC ≥ 1,800 cells/mm³
• Platelet count ≥ 100,000 cells/mm³
• Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Bilirubin normal
• AST and ALT < 2.5 times upper limit of normal
• PFTs including FEV1 ≥ 1.2 L/sec or ≥ 50% predicted (best value obtained prior to or after use of bronchodilator)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective protection
• No uncontrolled neuropathy ≥ grade 2
• Patients with post-obstructive pneumonia allowed
• No prior invasive malignancy, except nonmelanoma skin cancer, carcinoma in situ of the breast, oral cavity, or cervix, unless the patient has been disease-free for the past 3 years
• No prior severe infusion reaction to a monoclonal antibody
• No weight loss of ≥ 10% within the past 4 weeks
• No history of allergic reaction to paclitaxel or other taxanes, or to carboplatin
• No severe, active comorbidity, including any of the following:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or within past 30 days precluding study therapy
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • AIDS
• No significant history of uncontrolled cardiac disease, including any of the following:
  • Uncontrolled hypertension
  • unstable angina
  • Myocardial infarction within the past 6 months
  • Uncontrolled congestive heart failure
  • Cardiomyopathy with decreased ejection fraction

Expected Enrollment

Outcomes

Overall (Failure: death from any cause) survival

Progression-free survival (Failure: occurrence of local or regional progression, distant metastases, or death from any cause)
Local-regional failure (Failure: occurrence of local or regional progression)
Grade 3-5 esophagitis and pneumonitis adverse events as assessed by NCI CTCAE v3.0
Other grade 3-5 adverse events as assessed by NCI CTCAE v3.0
Death during or within 30 days of discontinuation of protocol treatment
Quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) and lung cancer subscale (LCS)
Patient-reported swallowing ability
Quality-adjusted survival based on EuroQoL (EQ5D)-derived health utility score
Correlation of tumor markers with overall survival, local-regional failure, and QOL
Prognostic and predictive effects of gross tumor volume on overall survival
Prognostic value of pre-treatment standardized uptake value (SUV) of PET scan in predicting survival, distant metastasis, and local-regional control

Outline

This is a multicenter study. Patients are stratified according to PET staging (yes vs no), radiotherapy technique (3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy), Zubrod performance status (0 vs 1), 4-dimensional CT planning utilization (yes vs no), and histology (squamous vs non-squamous). Patients are randomized to 1 of 4 treatment arms. (Arms II and IV closed to accrual effective 6/17/11)

• Arm I: Patients undergo standard dose radiotherapy 5 days a week for 6 weeks for a total of 60 Gy. Patients receive concurrent chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients also receive consolidation treatment of paclitaxel and carboplatin on days 64 and 85. Treatment repeats in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo high-dose radiotherapy 5 days per week for 7.5 weeks. Patient also receive concurrent paclitaxel and carboplatin as in Arm I on days 1, 8, 15, 22, 29, 36, and 43 . Patients also receive consolidation treatment comprising paclitaxel and carboplatin on days 71 and 92. (closed to accrual effective 6/17/11)

• Arm III: Patients undergo standard-dose radiotherapy 5 days a week for 6 weeks for a total of 60 Gy. Patients receive cetuximab in addition to concurrent chemotherapy as in Arm I. Treatment continues with chemoradiation and cetuximab on days 8, 15, 22, 29, 36, and 43. Patients receive consolidation treatment of cetuximab on days 50, 57, 64, 71, 78, 85, 92, 99, and 106 and paclitaxel and carboplatin on days 71 and 92.

• Arm IV: Patients undergo high-dose radiotherapy 5 days a week for 7.5 weeks for a total of 74 Gy. Patients receive cetuximab in addition to concurrent chemotherapy as in Arm I. Treatment continues with chemoradiation and cetuximab on days 8, 15, 22, 29, 36, 43, and 50. Patients receive consolidation treatment of cetuximab on days 57, 64, 71, 78, 85, 92, 99, 106, and 113 and paclitaxel and carboplatin on days 78 and 99. (closed to accrual effective 6/17/11)

Patients may undergo tumor tissue, blood, and urine collection periodically during study for tissue banking or biomarker correlative studies.

Patients may undergo quality-of-life assessment at baseline and periodically during study.

After completion of study therapy, patients are followed periodically for 5 years and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Jeffrey Bradley, MD, Principal investigator		Ph: 314-362-8525
Hak Choy, MD, Protocol co-chair		Ph: 214-645-7600; 866-460-4673 Email: Hak.Choy@UTSouthwestern.edu
Gregory Masters, MD, Protocol co-chair		Ph: 302-366-1200

North Central Cancer Treatment Group

Steven Schild, MD, Protocol chair		Ph: 480-301- Email: sschild@mayo.edu
Alex Adjei, MD, PhD, Protocol co-chair		Ph: 507-538-0268; 800-685-6825 Email: alex.adjei@roswellpark.org

Cancer and Leukemia Group B

Jeffrey Bogart, MD, Protocol chair		Ph: 315-464-5276; 877-464-8668 Email: bogartj@upstate.edu
Arthur William Blackstock, MD, Protocol co-chair		Ph: 336-713-6501; 800-446-2255
Mark Socinski, MD, Protocol co-chair		Ph: 919-966-4431 Email: socinski@med.unc.edu

Registry Information
Official Title		A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy with Concurrent and Consolidation Carboplatin/Paclitaxel +/- Cetuximab (IND #103444) in Patients with Stage IIIA/IIIB Non-Small Cell Lung Cancer
Trial Start Date		2007-11-27
Trial Completion Date		2014-01-27 (estimated)
Registered in ClinicalTrials.gov		NCT00533949
Date Submitted to PDQ		2007-08-22
Information Last Verified		2011-11-23
NCI Grant/Contract Number		CA21661

Back to Top