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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 cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. 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. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

Official Title

A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas

Details

OBJECTIVES:

Primary

  • Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve disease-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx.

Secondary

  • Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients.
  • Correlate the expression of epidermal growth factor receptor (EGFR) and its down-stream molecules with outcome in patients participating in this component of the trial.
  • Correlate pre-treatment PET scan findings with disease-free survival, overall survival, and local-regional control in patients participating in this component of the trial.
  • Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo either 3D-conformal radiotherapy or IMRT once or twice a day, 5 or 6 days a week, for 6 weeks. Patients also receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
  • Arm II: Patients receive cetuximab IV over 1-2 hours once in weeks 0-7. Beginning in week 1, patients also undergo radiotherapy and receive cisplatin as in arm I.

In both arms, patients with persistent nodal disease (any stage) (i.e., a residual palpable or radiographic abnormality) undergo neck dissection* approximately 9-10 weeks after completion of treatment.

NOTE: *A neck dissection is optional for patients with multiple lymph nodes or lymph nodes > 3 cm in diameter who achieve a complete clinical and radiographic response in the neck.

Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years.

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

PROJECTED ACCRUAL: Approximately 720 patients will be accrued for this study.

Keywords

Head and Neck Cancer stage III squamous cell carcinoma of the hypopharynx stage IV squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx Head and Neck Neoplasms Cisplatin Cetuximab

Eligibility

For people ages 18 years and up

DISEASE CHARACTERISTICS:

  • Histologically proven (from primary lesion and/or lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx
  • Stage III or IV disease (T2, N2-3, M0; T3-4, any N, M0)
  • No distant metastases
  • The following primary tumor sites are excluded:
  • Oral cavity
  • Nasopharynx
  • Sinuses
  • Salivary glands

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute neutrophil count (ANC) ≥ 1,800/mm3

  • Platelets ≥ 100,000/mm3

  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
  • Bilirubin ≤ 1.5 mg/dL (Gilbert's disease as the sole cause of elevated bilirubin may be allowed at the discretion of the principal investigator)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 times the upper limit of normal
  • Serum creatinine ≤ 1.5 mg/dL
  • Creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment)
  • No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
  • No unstable angina and/or congestive heart failure requiring hospitalization in past 6 months
  • Left ventricular ejection fraction ≥ 45%
  • No transmural myocardial infarction within the last 6 months
  • No acute bacterial or fungal infection requiring intravenous antibiotics
  • No chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  • No acquired immune deficiency syndrome (AIDS)
  • HIV testing is not required for entry into this protocol
  • Protocol-specific requirements may also exclude immuno-compromised patients
  • No prior allergic reaction to the study drug(s)
  • No other uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures
  • No comorbidity of uncontrolled diabetes (i.e., symptomatic hyperglycemia)
  • No other severe active comorbidity

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy for the study cancer
  • Prior chemotherapy for a different cancer is allowed
  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • No initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease)
  • No radical or modified neck dissection
  • No prior therapy that specifically and directly targets the EGFR pathway

Locations

  • San Francisco General Hospital Medical Center
    San Francisco, California, 94110, United States
  • UCSF Helen Diller Family Comprehensive Cancer Center
    San Francisco, California, 94115, United States
  • California Pacific Medical Center - California Campus
    San Francisco, California, 94118, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, United States
  • Bay Area Breast Surgeons, Incorporated
    Oakland, California, 94609, United States
  • CCOP - Bay Area Tumor Institute
    Oakland, California, 94609, United States
  • Larry G Strieff MD Medical Corporation
    Oakland, California, 94609, United States
  • Tom K Lee, Incorporated
    Oakland, California, 94609, United States
  • Alta Bates Summit Comprehensive Cancer Center
    Berkeley, California, 94704, United States
  • Marin Cancer Institute at Marin General Hospital
    Greenbrae, California, 94904, United States
  • Sutter Health - Western Division Cancer Research Group
    Greenbrae, California, 94904, United States
  • Peninsula Medical Center
    Burlingame, California, 94010, United States
  • Doctors Medical Center - San Pablo Campus
    San Pablo, California, 94806, United States
  • East Bay Radiation Oncology Center
    Castro Valley, California, 94546, United States
  • Valley Medical Oncology Consultants - Castro Valley
    Castro Valley, California, 94546, United States
  • John Muir/Mt. Diablo Comprehensive Cancer Center
    Walnut Creek, California, 94598, 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
  • Sutter Solano Medical Center
    Vallejo, California, 94589, United States
  • Valley Medical Oncology
    Fremont, California, 94538, United States
  • Valley Medical Oncology Consultants - Pleasanton
    Pleasanton, California, 94588, United States
  • General Robert Huyser Cancer Center at David Grant Medical Center
    Travis AFB, California, 94535-1800, United States
  • Solano Radiation Oncology Center
    Vacaville, California, 95687, United States
  • University of California Davis Cancer Center
    Sacramento, California, 95817, United States
  • Mercy General Hospital
    Sacramento, California, 95819, 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
  • Radiation Oncology Centers - Cameron Park
    Cameron Park, California, 95682, United States
  • Auburn Radiation Oncology
    Auburn, California, 95603, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010-3000, United States
  • USC/Norris Comprehensive Cancer Center and Hospital
    Los Angeles, California, 90089-9181, United States
  • Virginia K. Crosson Cancer Center at St. Jude Medical Center
    Fullerton, California, 92835, 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
NCT00265941
Phase
Phase 3
Lead Scientist
Mack Roach
Study Type
Interventional
Last Updated
October 2016