Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00084318
First received: June 10, 2004
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Cisplatin and docetaxel may make the tumor cells more sensitive to radiation therapy. Combining a monoclonal antibody with chemoradiotherapy and giving them after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying adjuvant cetuximab given together with chemoradiotherapy using cisplatin to see how well it works compared to adjuvant cetuximab given together with chemoradiotherapy using docetaxel in treating patients with resected stage III or stage IV squamous cell carcinoma (cancer) or lymphoepithelioma of the head and neck.


Condition Intervention Phase
Head and Neck Cancer
Biological: cetuximab
Drug: cisplatin
Drug: docetaxel
Procedure: adjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: From randomization to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From randomization to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment tolerance [ Time Frame: From start of treatment to end of treatment ] [ Designated as safety issue: Yes ]
  • Frequency of toxicity (grade 5 and acute non-hematologic grade 4) [ Time Frame: From start of treatment to last follow-up ] [ Designated as safety issue: Yes ]
  • Frequency of other acute and late toxicity [ Time Frame: From start of treatment to last follow-up ] [ Designated as safety issue: Yes ]
  • Local-regional control [ Time Frame: From randomization to 2 years ] [ Designated as safety issue: No ]
  • Correlation of EGFR (total and phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and cyclin B1 expression with local-regional control, and overall and disease-free survival [ Time Frame: From randomization to last follow-up ] [ Designated as safety issue: No ]

Enrollment: 238
Study Start Date: April 2004
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab, cisplatin and radiation therapy (RT)
Week1: Cetuximab loading dose. Weeks 2-7: 60 Gy (2 Gy/day) plus cetuximab and cisplatin weekly.
Biological: cetuximab Drug: cisplatin Procedure: adjuvant therapy Radiation: radiation therapy
Experimental: Cetuximab, docetaxel and RT
Week 1: Cetuximab loading dose. Weeks 2-7: 60Gy (2Gy/day) plus cetuximab and docetaxel weekly.
Biological: cetuximab Drug: docetaxel Procedure: adjuvant therapy Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

Primary

  • Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin.

Secondary

  • Compare the safety and efficacy of these regimens in these patients.
  • Compare locoregional control and overall survival rates in patients treated with these regimens.
  • Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk [i.e., ≥ 2 positive nodes or extracapsular nodal extension]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7).
  • Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7).

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed squamous cell carcinoma of the head and neck meeting the following criteria:

    • Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses)
    • Gross total resection must be completed within 7 weeks of randomization, with pathology demonstrating one or more of the following risk factors:

      • Histologic extracapsular nodal extension
      • Histologic involvement of ≥ 2 regional lymph nodes
      • Invasive cancer seen on microscopic evaluation of the resection margin, with no evidence of gross tumor residual. or lymphoepithelioma of the oral cavity, oropharynx, larynx, or hypopharynx
      • Tonsillar cancer patients who undergo transoral excision of all gross tumor are eligible provided extracapsular nodal extension or involvement of ≥ 2 regional lymph nodes is histologically confirmed
    • Stage III or IV disease after gross total resection completed within the past 7 weeks
  • No evidence of distant metastases
  • No synchronous or concurrent head and neck primary tumors

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 2,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin > 8.0 g/dL

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), and alkaline phosphatase meeting 1 of the following parameters:

    • Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN
    • Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
    • Alkaline phosphatase ≤ 5 times ULN AND AST or ALT ≤ ULN

Renal

  • Creatinine ≤ 1.5 mg/dL

Cardiovascular

  • No unstable angina
  • No uncontrolled hypertension
  • No myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty)
  • No uncontrolled arrhythmia
  • No congestive heart failure
  • No more than 2 heart-related hospitalizations within the past year
  • No other active cardiac disease

Pulmonary

  • No more than 2 hospitalizations for chronic obstructive pulmonary disease within the past year

Neurologic

  • No pre-existing peripheral neuropathy ≥ grade 2
  • No uncontrolled seizure disorder
  • No active neurological disease

Other

  • No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
  • No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
  • No other concurrent illness that would preclude study participation
  • No concurrent psychiatric illness that would preclude study participation
  • No other concurrent physical condition (e.g., infectious disease) that would preclude study participation
  • No prisoners
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior anti-epidermal growth factor receptor antibody therapy

Chemotherapy

  • More than 3 years since prior cytotoxic chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior head and neck radiotherapy
  • No concurrent intensity-modulated radiotherapy

Surgery

  • See Disease Characteristics

Other

  • No prior tyrosine kinase inhibitor therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00084318

  Show 160 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Paul M. Harari, MD University of Wisconsin, Madison
Study Chair: Merrill S. Kies, MD M.D. Anderson Cancer Center
Study Chair: Jeffrey N. Myers, MD, PhD, FACS M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Harari PM, Harris J, Kies MS, et al.: Phase II randomized trial of surgery followed by chemoradiation plus cetuximab for high-risk squamous cell carcinoma of the head and neck (RTOG 0234). [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-22, S13, 2007.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00084318     History of Changes
Obsolete Identifiers: NCT00414674
Other Study ID Numbers: RTOG-0234, CDR0000360850
Study First Received: June 10, 2004
Last Updated: October 21, 2013
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 oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage III lymphoepithelioma of the oropharynx
stage IV lymphoepithelioma of the oropharynx

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Docetaxel
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014