Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
NRG Oncology Foundation, Inc.
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00265941
First received: December 14, 2005
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Biological: cetuximab
Drug: cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs after 434 failures have been reported. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after 434 failures have been reported. ] [ Designated as safety issue: No ]
  • Local-regional control (LRC) [ Time Frame: From randomization to date of failure (local or regional progression) or distant progression or death or last follow-up. Analysis occurs after 434 failures have been reported. ] [ Designated as safety issue: No ]
  • Mucositis toxicity ≥ grade 3 [ Time Frame: From start of treatment to last follow-up ] [ Designated as safety issue: Yes ]
  • Other toxicity ≥ grade 3 [ Time Frame: From start of treatment to last follow-up ] [ Designated as safety issue: Yes ]
  • Protocol treatment delivery [ Time Frame: From start of treatment to end of treatment ] [ Designated as safety issue: No ]
  • Death ≤ 30 days after discontinuation of protocol treatment [ Time Frame: From start of treatment to 30 days after the end of treatment ] [ Designated as safety issue: Yes ]
  • Quality of life as measured by Performance Status Scale for Head and Neck Cancer and the European Quality of Life questionnaire (EQ-5D) [ Time Frame: From randomization to 5 years ] [ Designated as safety issue: No ]
  • Quality of life as measured by Functional Assessment of Cancer Therapy-General version [ Time Frame: From randomization to 5 years ] [ Designated as safety issue: No ]
  • Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., MAPK, AKT, Stat-3, PKC) with DFS, OS, and LRC [ Time Frame: From randomization to date of death or last follow-up ] [ Designated as safety issue: No ]
    Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., mitogen-activated protein kinase (MAPK), serine/threonine-specific protein kinase (AKT), Stat-3, PKC) with DFS, OS, and LRC

  • Correlation of pre-treatment positron emission tomography (PET)/CT scan findings with DFS, OS, and LRC [ Time Frame: From randomization to date of death or last follow-up ] [ Designated as safety issue: No ]
  • Correlation of post-treatment PET/CT scan findings with pathologic nodal complete response and nodal relapse rate at 2 years in clinical N2-3 patients [ Time Frame: From randomization to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 720
Study Start Date: November 2005
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
Drug: cisplatin
Given IV
Experimental: Arm II
Patients receive cetuximab IV over 1-2 hours once in weeks 0-7 and cisplatin as in arm I.
Biological: cetuximab
Given IV
Drug: cisplatin
Given IV

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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/mm^3
  • Platelets ≥ 100,000/mm^3
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00265941

  Show 372 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
NRG Oncology Foundation, Inc.
Investigators
Principal Investigator: David Rosenthal, MD M.D. Anderson Cancer Center
Study Chair: Phuc Felix Nguyen-Tan, MD CHUM Hospital Notre Dame
  More Information

Additional Information:
Publications:
Ang K, Zhang Q, Rosenthal DI, et al.: A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas (HNC). [Abstract] J Clin Oncol 29 (Suppl 15): A-5500, 2011.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00265941     History of Changes
Other Study ID Numbers: RTOG 0522, CDR0000458049, NCI-2009-00729
Study First Received: December 14, 2005
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014