Clinical Trials /

Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer

NCT02177838

Description:

This pilot clinical trial studies cetuximab and radiation therapy in treating patients with stage III-IV head and neck cancer. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. 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, by stopping them from dividing, or by stopping them from spreading. Giving cetuximab or cisplatin together with radiation therapy may kill more tumor cells.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer
  • Official Title: Selecting for Cetuximab Responders in Advanced Head and Neck SCC

Clinical Trial IDs

  • ORG STUDY ID: 031204
  • SECONDARY ID: NCI-2014-01303
  • SECONDARY ID: 031204
  • SECONDARY ID: P30CA072720
  • NCT ID: NCT02177838

Conditions

  • Stage III Squamous Cell Carcinoma of the Hypopharynx
  • Stage III Squamous Cell Carcinoma of the Larynx
  • Stage III Squamous Cell Carcinoma of the Oropharynx
  • Stage III Verrucous Carcinoma of the Larynx
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IVA Squamous Cell Carcinoma of the Larynx
  • Stage IVA Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Verrucous Carcinoma of the Larynx
  • Stage IVB Squamous Cell Carcinoma of the Larynx
  • Stage IVB Squamous Cell Carcinoma of the Oropharynx
  • Stage IVB Verrucous Carcinoma of the Larynx
  • Tongue Cancer

Interventions

DrugSynonymsArms
cetuximabC225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225Treatment (cetuximab, cisplatin, EBRT)
cisplatinCACP, CDDP, CPDD, DDPTreatment (cetuximab, cisplatin, EBRT)

Purpose

This pilot clinical trial studies cetuximab and radiation therapy in treating patients with stage III-IV head and neck cancer. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. 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, by stopping them from dividing, or by stopping them from spreading. Giving cetuximab or cisplatin together with radiation therapy may kill more tumor cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 2 year (yr) locoregional control in cetuximab responders.

      SECONDARY OBJECTIVES:

      I. Assess secondary clinical endpoints such as the percent of patients receiving neoadjuvant
      cetuximab who progress by computed tomography (CT) Response Evaluation Criteria in Solid
      Tumors (RECIST) 1.1 criteria during the neoadjuvant cetuximab, the 2 yr locoregional control
      for non-responders to neoadjuvant cetuximab, and the complete response rate to positron
      emission tomography (PET)/computed tomography (CT) scan 3 months after the completion of
      radiation therapy for both responders and for non-responders to neoadjuvant cetuximab.

      II. Analyze the relationship of known deoxyribonucleic acid (DNA) mutations in tumor per the
      FoundationOne genomic profile, and correlate to clinical endpoints such as locoregional
      control.

      II. Analyze any changes in protein production at the tumor in response to 3 weeks of
      cetuximab.

      III. Analyze any changes in protein production at the skin in response to 3 weeks of
      cetuximab.

      IV. To investigate whether the tumor imaging characteristics including anatomical and
      molecular parameters evaluated by PET/CT, either alone or combined with other biomarkers can
      attribute to the better prediction for the clinical outcomes, as the response to neoadjuvant
      cetuximab; and the final clinical endpoint, the 2-year local regional controls.

      OUTLINE:

      Patients receive cetuximab intravenously (IV) over 60-120 minutes for 3 weeks. Patients then
      undergo external beam radiation therapy (EBRT) over 6-7 weeks. Patients achieving response
      continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to
      achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of
      radiation therapy.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cetuximab, cisplatin, EBRT)ExperimentalPatients receive cetuximab IV over 60-120 minutes for 3 weeks. Patients then undergo EBRT over 6-7 weeks. Patients achieving response continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of radiation therapy.
  • cetuximab
  • cisplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven squamous cell carcinoma of the oropharynx, hypopharynx or larynx

          -  Stage III/IVa/b squamous cell carcinoma (SCC) by American Joint Committee on Cancer
             (AJCC) 7 criteria (advanced, but not metastatic)

          -  Patients must give informed consent

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =<
             2

          -  Platelets >= 100,000/uL

          -  Absolute neutrophil count (ANC) >= 1,500/uL

          -  Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)

          -  Total bilirubin < 2 X institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3 X institutional ULN

          -  Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as
             determined by 24 hour collection or estimated by Cockcroft-Gault formula

          -  Estimated life expectancy of at least 12 weeks

          -  Negative pregnancy test

        Exclusion Criteria:

          -  Patients may not have received previous therapy for their head and neck SCC, including
             chemotherapy, radiation therapy, or surgery beyond biopsy

          -  Second primary malignancy; exceptions are 1) patient had a second primary malignancy
             but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g.
             in situ carcinoma of the cervix), 3) non-melanomatous carcinoma of the skin

          -  Patients with metastatic disease beyond the neck and supraclavicular region will be
             excluded

          -  Serious concomitant systemic disorders (including active infections) that would
             compromise the safety of the patient or compromise the patient's ability to complete
             the study, at the discretion of the investigator; this includes scleroderma

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to cetuximab or cisplatinum or other agents used in the study

          -  Women who are pregnant; women of childbearing age must agree to undergo a pregnancy
             test prior to therapy and to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) prior to study entry, for the duration of study
             participation and for 6 months after; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Patients with human immunodeficiency virus (HIV) infection are not automatically
             excluded, but must meet the following criteria: cluster of differentiation (CD)4 count
             is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active
             anti-retroviral therapy (HAART) is allowed

          -  Patients who have had either myocardial infarction, coronary artery bypass graft,
             coronary artery stenting, hospital admission for heart related issues such as
             congestive heart failure or arrhythmia within the last 3 months, will not be allowed
             on protocol

          -  Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events
             [CTCAE], version [v]. 4):

               -  Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5
                  mg/dl (> 3.1 mmol/L) despite intervention to normalize levels

               -  Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite
                  intervention to normalize levels

               -  Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels

               -  Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Locoregional control in cetuximab responders
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percent of patients who progress during neoadjuvant cetuximab by CT RECIST 1.1 criteria
Time Frame:Day 14-21 after the first dose of cetuximab
Safety Issue:
Description:Will be descriptive.
Measure:Locoregional control for non-responders to neoadjuvant cetuximab
Time Frame:2 years
Safety Issue:
Description:Will be descriptive.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rutgers, The State University of New Jersey

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