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Trial record 1 of 1 for:    RTOG 0617
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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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00533949
First Posted: September 24, 2007
Last Update Posted: May 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

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.


Condition Intervention Phase
Lung Cancer Radiation Toxicity Biological: Cetuximab Drug: Carboplatin Drug: Paclitaxel Radiation: 60 Gy RT Radiation: 74 Gy RT Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
This study was revised 06/18/08 to a 2x2 factorial design to evaluate the addition of cetuximab to the radiation therapy regimens.
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Analysis occurs after 50 months of accrual and an additional 18 months of follow-up, such that patients are followed at least 18 months from randomization. ]
    Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: Analysis occurs after 50 months of accrual and an additional 18 months of follow-up, such that patients are followed at least 18 months from randomization. ]
    A failure for progression-free survival (PFS) is the first occurrence of local or regional progression, distant metastases, or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Time is measured from the date of randomization to the date of first failure. Patients without failure are censored at the date of last follow-up.

  • Local-regional Failure (Reported as Two-year Estimates) [ Time Frame: Analysis occurs after 50 months of accrual and an additional 18 months of follow-up, such that patients are followed at least 18 months from randomization. ]
    A failure for local-regional failure is the first occurrence of local or regional progression. Time is measured from the date of randomization to the date of first failure. Patients alive without local or regional failure at the time of last follow-up are censored. Patients who died without local or regional failure are considered as having competing risk at the time of death. Local-regional failure was estimated by the cumulative incidence method and 2 year estimates are reported.

  • Percentage of Participants With Grade 3-5 Esophagitis and Pneumonitis Adverse Events as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 [ Time Frame: Analysis occurs after 50 months of accrual and an additional 18 months of follow-up, such that patients are followed at least 18 months from randomization. ]
    Treatment-related esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.

  • Percentage of Participants With Other Grade 3-5 Adverse Events as Assessed by NCI CTCAE v3.0 [ Time Frame: Analysis occurs 50 months of accrual and an additional 18 months of follow-up, such that patients are followed at least 18 months from randomization. ]
    Treatment-related adverse events other than esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.

  • Death During or Within 30 Days of Discontinuation of Protocol Treatment [ Time Frame: From start of treatment to 24 months. ]
    Deaths regardless of cause and occuring during or within 30 days of discontinuation of protocol treatment were evaluated.

  • Percentage of Patients With Decline From Baseline to 3 Months in the Lung Cancer Subscale (LCS) of the Functional Assessment of the Cancer Therapy Trial Outcome Index (FACT-TOI). [ Time Frame: At baseline and 3 months. ]
    A decline of 2 points in the LCS from baseline to 3 months was considered a clinically meaningful change indicating a decline in quality of life. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.

  • Patient-reported Swallowing Ability [ Time Frame: From start of treatment to 24 months. ]
  • Quality-adjusted Survival Based on EuroQoL (EQ5D)-Derived Health Utility Score [ Time Frame: From start of treatment to 24 months. ]
  • Correlation of Tumor Markers With Overall Survival, Local-regional Failure, and QOL [ Time Frame: Analysis occurs after 339 deaths have been reported, estimated at 5.6 years from start of study, unless a futility bound is crossed prior to that. ]
    Biomarker data has not yet been obtained and therefore this outcome measure cannot yet be reported.

  • Prognostic and Predictive Effects of Gross Tumor Volume on Overall Survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after 339 deaths have been reported. ]
  • Prognostic Value of Pre-treatment Standardized Uptake Value (SUV) of Positron Emission Tomography (PET) Scan in Predicting Survival, Distant Metastasis, and Local-regional Control [ Time Frame: From randomization to date of failure (either local or regional), death or last follow-up. Analysis occurs after 339 deaths have been reported. ]

Enrollment: 544
Study Start Date: November 2007
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 60 Gy RT
60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Drug: Carboplatin

Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.

Other Name: Paraplatin
Drug: Paclitaxel

Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.

Other Names:
  • Taxol
  • Abraxane
Radiation: 60 Gy RT
Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 30 fractions over the course of 6 weeks.
Other Name: RT
Experimental: 74 Gy RT
74 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Drug: Carboplatin

Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.

Other Name: Paraplatin
Drug: Paclitaxel

Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.

Other Names:
  • Taxol
  • Abraxane
Radiation: 74 Gy RT
Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 37 fractions over the course of 7.5 weeks.
Experimental: 60 Gy RT + Cetuximab
60 Gy Radiation therapy with concurrent cetuximab, paclitaxel, and carboplatin followed by consolidation cetuximab, paclitaxel, and carboplatin
Biological: Cetuximab
Loading dose: 400 mg/m2, IV, one week prior to start of radiation therapy (RT). Then, beginning day 1 of RT, 250 mg/m2, IV, weekly; for 60 Gy arm for 15 weeks, for 74 Gy arm for 16 weeks.
Other Name: Erbitux
Drug: Carboplatin

Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.

Other Name: Paraplatin
Drug: Paclitaxel

Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.

Other Names:
  • Taxol
  • Abraxane
Radiation: 60 Gy RT
Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 30 fractions over the course of 6 weeks.
Other Name: RT
Experimental: 74 Gy RT + Cetuximab
74 Gy Radiation therapy with concurrent cetuximab, paclitaxel, and carboplatin followed by consolidation cetuximab, paclitaxel, and carboplatin
Biological: Cetuximab
Loading dose: 400 mg/m2, IV, one week prior to start of radiation therapy (RT). Then, beginning day 1 of RT, 250 mg/m2, IV, weekly; for 60 Gy arm for 15 weeks, for 74 Gy arm for 16 weeks.
Other Name: Erbitux
Drug: Carboplatin

Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.

Other Name: Paraplatin
Drug: Paclitaxel

Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well.

Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.

Other Names:
  • Taxol
  • Abraxane
Radiation: 74 Gy RT
Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 37 fractions over the course of 7.5 weeks.

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00533949


  Show 213 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
NRG Oncology
Investigators
Principal Investigator: Jeffrey Bradley, MD Mallinckrodt Institute of Radiology at Washington University Medical Center
Study Chair: Hak Choy, MD Simmons Cancer Center
Study Chair: Gregory A. Masters, MD CCOP - Christiana Care Health Services
Study Chair: Steven E. Schild, MD Mayo Clinic
Study Chair: Alex A. Adjei, MD, PhD Roswell Park Cancer Institute
Study Chair: Jeffrey A. Bogart, MD State University of New York - Upstate Medical University
Study Chair: Arthur William Blackstock, MD Wake Forest University Health Sciences
Study Chair: Mark A. Socinski, MD UNC Lineberger Comprehensive Cancer Center
Study Chair: George Blumenschein, MD M.D. Anderson Cancer Center
Study Chair: Ritsuko Komaki, MD M.D. Anderson Cancer Center
Study Chair: Jeff Sloan, PhD, HSR Mayo Clinic
Study Chair: Mark Dobelbower, MD PhD University of Alabama Medical Center
Study Chair: Tien Hoang, MD University of Wisconsin, Madison
Study Chair: Ken Forster, PhD H. Lee Moffitt Cancer Center
Study Chair: Benjamin Movsas, MD Henry Ford Hospital
Study Chair: Joe Y. Chang, MD PhD M.D. Anderson Cancer Center
Study Chair: Joseph O. Deasy, PhD Memorial Sloan Kettering Cancer Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00533949     History of Changes
Other Study ID Numbers: RTOG 0617
CDR0000564240
NCCTG-N0628
CALGB-30609
NCI-2013-01762 ( Registry Identifier: CTRP (Clinical Trials Reporting Program) )
First Submitted: September 20, 2007
First Posted: September 24, 2007
Results First Submitted: January 17, 2017
Results First Posted: May 5, 2017
Last Update Posted: May 5, 2017
Last Verified: March 2017

Keywords provided by Radiation Therapy Oncology Group:
radiation toxicity
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Radiation Injuries
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Wounds and Injuries
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action