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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy with or without cetuximab in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying high-dose or standard-dose radiation therapy given together with chemotherapy with or without cetuximab to see how well they work in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.

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

Details

OBJECTIVES:

Primary

  • 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.
  • To compare the overall survival of patients treated with versus without cetuximab in the setting of concurrent chemotherapy

Secondary

  • To compare progression-free survival and local-regional tumor control in patients treated with these regimens.
  • To compare the toxicity of high- versus standard-dose conformal radiotherapy and concurrent chemotherapy with versus without cetuximab in these patients.
  • To investigate the prognostic and predictive effects of gross tumor volume on overall survival of patients treated with these regimens.
  • To compare the quality of life of patients treated with these regimens.
  • To correlate outcomes (i.e., survival, toxicity, or QOL) in these patients with biological parameters.
  • To analyze the predictive value of pre-treatment standardized uptake value (SUV) of positron emission tomography (PET) scan in predicting survival, distant metastasis, and local-regional control in patients treated with these regimens.
  • 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.
  • To prospectively collect and bank tissue, blood, and urine specimens for future biomarker analyses in predicting clinical outcome in patients treated with these regimens.
  • To investigate associations between epidermal growth factor receptor (EGFR) expression and toxicity, response, overall survival, and progression-free survival.

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), 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.
  • 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.

Keywords

Lung Cancer Radiation Toxicity stage IIIA non-small cell lung cancer stage IIIB non-small cell lung cancer Paclitaxel Albumin-Bound Paclitaxel Carboplatin Cetuximab

Eligibility

For people ages 18 years and up

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

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute neutrophil (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
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal
  • Pulmonary Function Test (PFTs) including forced expiratory volume at 1 sec. (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
  • Patients must speak English or Spanish in order to complete the mandatory EORTC QLQ-30 and PRO-CTCAE, which are only available in certain languages
  • 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

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 white blood cell (WBC) growth factors (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF]) given during radiotherapy or prophylactically during consolidation chemotherapy

Locations

  • Saint Agnes Cancer Center at Saint Agnes Medical Center
    Fresno, California, 93720, United States
  • Cancer Care Center at John Muir Health - Concord Campus
    Concord, California, 94524-4110, United States
  • Stanford Cancer Center
    Stanford, California, 94305-5824, United States
  • Saint Helena Hospital
    Saint Helena, California, 94574, United States
  • University of California Davis Cancer Center
    Sacramento, California, 95817, United States
  • Radiological Associates of Sacramento Medical Group, Incorporated
    Sacramento, California, 95815, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Mercy Cancer Center at Mercy San Juan Medical Center
    Carmichael, California, 95608, United States
  • Radiation Oncology Center - Roseville
    Roseville, California, 95661, United States
  • Enloe Cancer Center at Enloe Medical Center
    Chico, California, 95926, United States
  • Feather River Hospital Cancer Center
    Paradise, California, 95969, United States
  • Renown Institute for Cancer at Renown Regional Medical Center
    Reno, Nevada, 89502, United States
  • Saint Mary's Regional Medical Center
    Reno, Nevada, 89503, United States
  • St. Joseph Hospital Regional Cancer Center - Orange
    Orange, California, 92868, United States
  • CCOP - Nevada Cancer Research Foundation
    Las Vegas, Nevada, 89106, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Radiation Therapy Oncology Group
ID
NCT00533949
Phase
Phase 3
Lead Scientist
Sue Yom
Study Type
Interventional
Last Updated
March 1, 2017