Clinical Trials /

Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

NCT03383094

Description:

The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).

Related Conditions:
  • Head and Neck Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
  • Official Title: Phase II Randomized Trial of Radiotherapy With Concurrent and Adjuvant Pembrolizumab (Keytruda®) Versus Concurrent Chemotherapy in Patients With Advanced/Intermediate-Risk p16+ Head and Neck Squamous Cell Carcinoma (KEYCHAIN)

Clinical Trial IDs

  • ORG STUDY ID: 170862
  • NCT ID: NCT03383094

Conditions

  • Head and Neck Squamous Cell Carcinoma
  • Cancer
  • Cancer of Head and Neck
  • Cancer, Advanced
  • Cancer, Metastatic
  • Tumor
  • Tumor Recurrence
  • Tumor Neck
  • Tumor Metastasis
  • Oral Cancer
  • Oropharyngeal Cancer
  • Oropharynx Cancer
  • Oropharynx Cancer, Stage III
  • Oropharynx Cancer, Recurrent
  • Oropharynx Cancer, Metastatic

Interventions

DrugSynonymsArms
PembrolizumabImmunotherapyExperimental-Radiotherapy/pembrolizumab
CisplatinChemotherapyControl-radiotherapy/cisplatin

Purpose

The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).

Detailed Description

      This study is a prospective, multi-institutional, open-label, randomized phase II trial that
      will evaluate the efficacy of concurrent and adjuvant pembrolizumab with radiation therapy
      (RT) versus RT plus cisplatin in intermediate/high-riskp16-positive locoregionally advanced
      head and neck squamous cell carcinoma (HNSCC). The primary endpoint is progression-free
      survival (PFS).
    

Trial Arms

NameTypeDescriptionInterventions
Control-radiotherapy/cisplatinActive ComparatorIntensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent cisplatin 100 mg/m2 every 3 weeks for 3 cycles (7 weeks)
  • Cisplatin
Experimental-Radiotherapy/pembrolizumabExperimentalIntensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent and adjuvant pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  p16-positive squamous cell carcinoma of the pharynx, larynx or oral cavity

          -  High-Intermediate Risk Disease, defined as:

               -  T1-T3 N2 M0 or T3 N1 M0 or any stage III (T4 or N3) p16+ squamous cell carcinoma
                  of the oropharynx (AJCC 8th edition staging system)

               -  T1-2 N1-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the
                  hypopharynx or larynx

               -  T1-2 N2-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the
                  nasopharynx

               -  Inoperable T4 N0-3 M0 (stage IVA-IVB) p16+ squamous cell carcinoma of the oral
                  cavity

          -  Measurable disease based on RECIST 1.1

          -  Adequate hematologic function within 28 days prior to registration

          -  Adequate renal and hepatic function

          -  Female subject of childbearing potential should have a negative pregnancy test

          -  Female subjects of childbearing potential must agree to use an adequate method of
             contraception for the course of the study

          -  Male subjects must agree to use an adequate method of contraception for the course of
             the study

        Exclusion Criteria:

          -  Prior malignancy within the past 3 years (except non-melanomatous skin cancer and
             early stage treated prostate cancer);

          -  Prior head and neck radiation, chemotherapy, or immunotherapy;

          -  Prior oncologic (radical) surgery to the primary site;

          -  Documented evidence of distant metastases;

          -  Severe, active co-morbidity defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months;

               -  Transmural myocardial infarction within the last 6 months;

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration;

               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within 30 days of
                  registration;

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;
                  note, however, that HIV testing is not required for entry into this protocol.

          -  Any medical or psychiatric illness, which, in the opinion of the principal
             investigator, would compromise the patient's ability to tolerate this treatment;

          -  Psychiatric/social situations that would limit compliance with study requirements

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Known history of, or any evidence of active, non-infectious pneumonitis.

          -  Active infection requiring systemic therapy.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:progression-free survival (PFS)
Time Frame:3 years
Safety Issue:
Description:time from randomization to progression/relapse or death from any cause.

Secondary Outcome Measures

Measure:overall survival
Time Frame:3 years
Safety Issue:
Description:time from randomization to death from any cause
Measure:Acute toxicity
Time Frame:3 months
Safety Issue:
Description:Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires
Measure:Late toxicity
Time Frame:3 years
Safety Issue:
Description:Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires
Measure:Patterns of failure
Time Frame:3 years
Safety Issue:
Description:Local and regional and distant recurrence of cancer and causes of death from competing events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loren Mell, MD

Trial Keywords

  • cancer
  • Head and Neck
  • Pembrolizumab
  • Cisplatin
  • Radiotherapy
  • Head and Neck Squamous Cell Carcinoma
  • p16+
  • immunotherapy
  • pd-1
  • chemotherapy
  • T1
  • T2
  • T3
  • N2
  • M0
  • T4
  • N3
  • N1

Last Updated