Phase II Study of Concurrent C225, Cisplatin and Radiation in Stage IV Squamous Cell Carcinoma of the Head and Neck

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00096174
First received: November 9, 2004
Last updated: November 30, 2012
Last verified: November 2012
  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, 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. Cetuximab may make the tumor cells more sensitive to radiation therapy and chemotherapy. Giving monoclonal antibody therapy together with chemoradiotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab and cisplatin together with radiation therapy works in treating patients with locally advanced or regional stage IV head and neck cancer that cannot be removed by surgery.


Condition Intervention Phase
Head and Neck Cancer
Biological: cetuximab C225
Drug: cisplatin
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of C225 (Erbitux or Cetuximab) in Combination With Cisplatin and Definitive Radiation in Unresectable Stage IV Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 2-year Progression-free Survival Rate [ Time Frame: assessed every 3 months for 2 years ] [ Designated as safety issue: No ]
    Two-year progression-free survival rate was defined as the proportion of patients that were alive progression-free two years after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 2-year progression-free survival was calculated in the 60 eligible and treated patients.


Secondary Outcome Measures:
  • 2-year Overall Survival Rate [ Time Frame: assessed very 3 months for 2 years ] [ Designated as safety issue: No ]
    Overall survival was defined as time from registration to death from any cause. Patients alive at last follow-up were censored. The 2-year overall survival rate was defined as the percentage of patients that were still alive two years after registration into the study. Kaplan-Meier estimate of 2-year overall survival was calculated in the 60 eligible and treated patients.

  • Overall Response Rate [ Time Frame: assessed after all chemoradiation therapy completed Week 9, then every 3 months on C225 maintenance therapy, and every 3 months for 2 years, every 6 months post-treatment 2 years from study entry ] [ Designated as safety issue: No ]
    Response was assessed per Response Evaluation in Solid Tumor (RECIST) criteria by physical assessment and CT. Overall response = complete response (CR) + partial response (PR). CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions, along with non-progressive disease of non-target lesions. Overall response rate (i.e., proportion of patients who had CR or PR) and the corresponding 90% confidence intervals were calculated for the 60 eligible and treated patients


Enrollment: 69
Study Start Date: December 2004
Estimated Study Completion Date: July 2016
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin, C225, Radiation
  • Cetuximab therapy: Patients receive an initial loading dose of cetuximab intravenously (IV) over 2 hours on day 1. Patients then receive cetuximab IV over 1 hour on days 8, 15, 22, 29, 36, 43, 50, and 57.
  • Chemoradiotherapy: Beginning on day 15 of cetuximab therapy, patients undergo radiotherapy once daily, 5 days a week, for at least 7 weeks. Patients also receive cisplatin IV over 1-2 hours on days 15, 36, and 57.
  • Cetuximab maintenance therapy: After the completion of chemoradiotherapy, patients continue to receive cetuximab IV over 1 hour once weekly for 6-12 months.
Biological: cetuximab C225
400 mg/m^2 IV over 120 minutes on Day 1, 250 mg/m^2 IV over 60 minutes on Day 8, then weekly
Other Names:
  • Cetuximab
  • Erbitux
Drug: cisplatin
75 mg/m^2 IV over 30-60 minutes starting day 15 every 3 weeks * 3 (Days 1, 22, and 43 of radiation therapy (RT))
Other Names:
  • Platinol
  • Platinol-AQ
  • CDDP
  • DDP
  • DACP
  • Platinum
  • cis-Platinum
Radiation: radiation therapy
RT 70 Gy / 35 starting Day 15, 200cGy / d * 7 weeks (35 fractions)

Detailed Description:

OBJECTIVES:

Primary

  • Determine 2-year progression-free survival in patients with unresectable locally advanced or regional stage IV squamous cell or undifferentiated carcinoma of the head and neck treated with cetuximab, cisplatin, and definitive radiotherapy.

Secondary

  • Determine response rate and overall survival in patients treated with this regimen.
  • Determine the toxic effects of this regimen in these patients.
  • Correlate epidermal growth factor receptor (EGFR) expression by immunohistochemistry, EGFR phosphorylation, map kinase, Akt, signal transducer and activator of transcription 3 (STAT3), and other tissue and serum tests with toxicity of this regimen and outcomes in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor site (hypopharynx vs. oropharynx vs. oral cavity vs. larynx), primary tumor stage (T1-3 vs. T4), and nodal status (N0 vs. N1 vs. N2-3).

  • Cetuximab therapy: Patients receive an initial loading dose of cetuximab IV over 2 hours on day 1. Patients then receive cetuximab IV over 1 hour on days 8, 15, 22, 29, 36, 43, 50, and 57.
  • Chemoradiotherapy: Beginning on day 15 of cetuximab therapy, patients undergo radiotherapy once daily, 5 days a week, for at least 7 weeks. Patients also receive cisplatin IV over 1-2 hours on days 15, 36, and 57.
  • Cetuximab maintenance therapy: After the completion of chemoradiotherapy, patients continue to receive cetuximab IV over 1 hour once weekly for 6-12 months.

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

Patients are followed every 6 months for 10 years.

ACCRUAL: A total of 69 patients were accrued for this study.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed squamous cell or undifferentiated carcinoma of the head and neck (excluding nasopharynx, paranasal sinus, and parotid gland)

    • Unresectable locally advanced or regional stage IV disease
    • No evidence of distant metastases
  • Must have demonstrable primary tumor site
  • Measurable disease
  • Unresectable disease

    • Meets the following criteria for unresectable disease by tumor site:

      • Hypopharynx, meeting 1 of the following criteria:

        • Extension across the midline of the posterior pharyngeal wall
        • Any evidence of fixation to the cervical spine
      • Larynx

        • Direct subglottic extension (>3cm) into surrounding muscle or skin
      • Oral cavity

        • Lesion precluding functional reconstruction
      • Base of tongue, meeting 1 of the following criteria:

        • Extension into the root of the tongue
        • Patient refuses total glossectomy
      • Tonsillar area, meeting 1 of the following criteria:

        • Extension into pterygoid area as manifested by x-ray or trismus
        • Extension across midline of pharyngeal wall
        • Direct extension into soft tissue of the neck
      • Unilateral neck node metastases fixed to carotid artery, mastoid, base of skull, or cervical spine with any of the above tumors
  • Patients requiring total glossectomy are eligible
  • Age>=18 years
  • ECOG Performance status of 0-1
  • Adequate hematologic, renal, and hepatic function obtained <=4 weeks prior to registration

    • Absolute neutrophil count ≥ 2,000/mm^3
    • Platelet count ≥ 100,000/mm^3
    • Hemoglobin ≥ 9.0 g/dL
    • Alkaline phosphatase ≤ 3 times normal
    • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤ 3 times normal
    • Bilirubin ≤ 1.5 mg/dL
    • Creatinine ≤ 1.2 mg/dL OR creatinine clearance ≥ 50 mL/min
  • Able to tolerate fluid load
  • At least 14 days since major surgery (including dental extraction) except percutaneous endoscopic gastrostomy (PEG) placement or mediport placement

Exclusion Criteria:

  • Pregnant or nursing
  • Fertile patients do not use effective contraception
  • Patients who refuse surgery but whose tumors are technically resectable OR whose tumors are unresectable for medical reasons are not eligible
  • Disease metastases below the clavicles or elsewhere (M1) or with a postoperative recurrence
  • Prior excisional surgery of head and neck tumor
  • Prior radiotherapy to the head and neck region
  • Prior chemotherapy
  • Prior drugs that target the epidermal growth factor receptor pathway
  • Prior chimerized or murine monoclonal antibody
  • Active systemic infection
  • Known allergy to murine proteins
  • Severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year
  • Myocardial infarction within the past 3 months
  • Uncontrolled congestive heart failure
  • Unstable or uncontrolled angina
  • Clinically apparent jaundice
  • Postoperative recurrence
  • Other malignancy within the past 3 years except resected basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other in situ tumors
  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: NCT00096174

Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Corey J. Langer, MD Fox Chase Cancer Center
  More Information

Additional Information:
Publications:
Langer CJ, Lee JW, Patel UA, et al.: Preliminary analysis of ECOG 3303: concurrent radiation (RT), cisplatin (DDP) and cetuximab (C) in unresectable, locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). [Abstract] J Clin Oncol 26 (Suppl 15): A-6006, 2008.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00096174     History of Changes
Other Study ID Numbers: CDR0000390923, U10CA021115, E3303
Study First Received: November 9, 2004
Results First Received: February 28, 2011
Last Updated: November 30, 2012
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma 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
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 21, 2014