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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
cetuximab C225
cisplatin
radiation therapy
Sponsored by
Eastern Cooperative Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Cisplatin, C225, Radiation

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    2-year Progression-free Survival Rate
    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
    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
    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

    Full Information

    First Posted
    November 9, 2004
    Last Updated
    June 15, 2023
    Sponsor
    Eastern Cooperative Oncology Group
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00096174
    Brief Title
    Phase II Study of Concurrent C225, Cisplatin and Radiation in Stage IV Squamous Cell Carcinoma of the Head and Neck
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Completed
    Study Start Date
    April 8, 2005 (Actual)
    Primary Completion Date
    July 2009 (Actual)
    Study Completion Date
    July 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Eastern Cooperative Oncology Group
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Head and Neck Cancer
    Keywords
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    69 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Cisplatin, C225, Radiation
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    cetuximab C225
    Other Intervention Name(s)
    Cetuximab, Erbitux
    Intervention Description
    400 mg/m^2 IV over 120 minutes on Day 1, 250 mg/m^2 IV over 60 minutes on Day 8, then weekly
    Intervention Type
    Drug
    Intervention Name(s)
    cisplatin
    Other Intervention Name(s)
    Platinol, Platinol-AQ, CDDP, DDP, DACP, Platinum, cis-Platinum
    Intervention Description
    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))
    Intervention Type
    Radiation
    Intervention Name(s)
    radiation therapy
    Intervention Description
    RT 70 Gy / 35 starting Day 15, 200cGy / d * 7 weeks (35 fractions)
    Primary Outcome Measure Information:
    Title
    2-year Progression-free Survival Rate
    Description
    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.
    Time Frame
    assessed every 3 months for 2 years
    Secondary Outcome Measure Information:
    Title
    2-year Overall Survival Rate
    Description
    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.
    Time Frame
    assessed very 3 months for 2 years
    Title
    Overall Response Rate
    Description
    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
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Corey J. Langer, MD
    Organizational Affiliation
    Fox Chase Cancer Center
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Citations:
    Citation
    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.
    Results Reference
    result

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

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