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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:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00084318
First received: June 10, 2004
Last updated: November 18, 2016
Last verified: November 2016
  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
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
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 ]
    Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization to 2 years ] [ Designated as safety issue: No ]
    Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).

  • Treatment Tolerance [ Time Frame: From start of treatment to end of treatment (protocol treatment lasts seven weeks). ] [ Designated as safety issue: Yes ]
    Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.

  • Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4) [ Time Frame: From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis. ] [ Designated as safety issue: Yes ]
    Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was >30%. [RTOG = Radiation Therapy Oncology Group]

  • Frequency of Other Acute and Late Toxicity [ Time Frame: From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis. ] [ Designated as safety issue: Yes ]
    Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.

  • Local-regional Control [ Time Frame: From randomization to 2 years ] [ Designated as safety issue: No ]
    Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).

  • 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 two years ] [ Designated as safety issue: No ]
    Biomarker data has not yet been obtained and therefore this outcome measure cannot yet be reported.


Enrollment: 238
Study Start Date: April 2004
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RT + cisplatin + cetuximab
Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.
Biological: cetuximab
400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.
Drug: cisplatin
30 mg/m^2 intravenously infused over over 60 minutes in weeks 2 through 7.
Radiation: radiation therapy
60 Gy (2 Gy once a day, 5 times a week)
Experimental: RT + docetaxel + cetuximab
Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Biological: cetuximab
400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.
Drug: docetaxel
15 mg/m^2 intravenously infused over 30 minutes in weeks 2 through 7.
Radiation: radiation therapy
60 Gy (2 Gy once a day, 5 times a week)

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   (Adult, Senior)
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.
      • 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
    • American Joint Committee on Cancer (AJCC) pathological stage III or IV
  • 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
  • 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

Surgery

  • See Disease Characteristics

Other

  • No prior tyrosine kinase inhibitor therapy
  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: NCT00084318

  Show 160 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
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

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
Results First Received: June 14, 2016
Last Updated: November 18, 2016
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
Cisplatin
Cetuximab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 06, 2016