Clinical Trials /

Pembrolizumab in Combination With Cisplatin and Intensity Modulated Radiotherapy (IMRT) in Head and Neck Cancer

NCT02777385

Description:

The study regimen consists of cisplatin and radiation for all patients, the standard treatment for head and neck cancer. All patients will also receive pembrolizumab (the study drug), and will be randomized to two treatment schedules: either pembrolizumab with cisplatin-radiation, or pembrolizumab after completing cisplatin-radiation. The goal of this research study is to learn which therapy order (adding pembrolizumab during vs. after cisplatin and radiation) may be more effective in treating head and neck cancer, as well as learn the side effects of these combinations.Pembrolizumab is an immune therapy, a drug that stimulates the immune system to fight cancer, and is FDA approved in lung cancer and melanoma. It is not currently FDA approved for head and neck cancer.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma of Unknown Primary
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Combination With Cisplatin and Intensity Modulated Radiotherapy (IMRT) in Head and Neck Cancer
  • Official Title: Randomized, Phase II Study Evaluating Concurrent or Sequential Fixed-Dose Pembrolizumab in Combination With Cisplatin and Intensity Modulated Radiotherapy in Intermediate or High Risk, Previously Untreated, Locally Advanced Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: 15-132
  • NCT ID: NCT02777385

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaArm 1
CisplatinPlatinolArm 1

Purpose

The study regimen consists of cisplatin and radiation for all patients, the standard treatment for head and neck cancer. All patients will also receive pembrolizumab (the study drug), and will be randomized to two treatment schedules: either pembrolizumab with cisplatin-radiation, or pembrolizumab after completing cisplatin-radiation. The goal of this research study is to learn which therapy order (adding pembrolizumab during vs. after cisplatin and radiation) may be more effective in treating head and neck cancer, as well as learn the side effects of these combinations.Pembrolizumab is an immune therapy, a drug that stimulates the immune system to fight cancer, and is FDA approved in lung cancer and melanoma. It is not currently FDA approved for head and neck cancer.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalCisplatin, Radiation, and Pembrolizumab started 3 weeks after completion of cisplating and radiation.
  • Pembrolizumab
  • Cisplatin
Arm 2ExperimentalCisplatin and Radiation and Pembrolizumab given 1 week prior to the start of cisp/radiation and given every 3 weeks
  • Pembrolizumab
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent

          -  If a woman of childbearing potential, documentation of negative pregnancy

          -  Histologically-confirmed head and neck squamous cell carcinoma with no evidence of
             distant metastasis. The primary site may be the oral cavity, oropharynx, larynx, or
             hypopharynx. Patients with squamous cell carcinoma of unknown primary, metastatic to
             cervical lymph nodes, are permitted to enroll.

          -  High risk or intermediate risk disease, defined below. Staging evaluation should be
             determined by imaging studies and complete head and neck exam in accordance with the
             American Joint committee on Cancer Staging Manual, 7th edition.

             o High risk patient must meet one of the following criteria:

          -  Surgically unresectable oral cavity. Patients who are technically resectable but
             refuse surgery due to morbidity (eg. total glossectomy) are also eligible. Medically
             inoperable patients are not eligible.

          -  Larynx: T4 any N; T2-3 and ≥ N2a

          -  Hypopharynx: T1-2N1-3 or T3-4N0-3

          -  Oropharynx: p16(-) AND T3-4 or ≥ N2a

          -  Unknown primary: p16(-) AND ≥ N2a

             o Intermediate risk patients must meet one of the following criteria:

          -  Oropharynx: p16(+) AND one of the following

          -  T3 or ≥ N2a AND ≥ 10 pack-years tobacco exposure (see Tobacco Assessment Form,
             Appendix A)

          -  T4 or N3 disease irrespective of tobacco exposure

          -  Unknown primary: p16(+) AND one of the following

          -  ≥ N2a AND ≥ 10 pack-years tobacco exposure

          -  N3 disease irrespective of tobacco exposure

          -  Patients must be untreated with curative-intent surgery for current diagnosis of Stage
             III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites is
             permitted.

               -  Diagnostic simple tonsillectomy is permitted, provided patient has
                  RECIST-measurable nodal disease.

               -  Patients with a second HNSCC primary tumor are eligible for this study, provided
                  more than 2 years have elapsed since the first diagnosis of HNSCC, the original
                  tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy),
                  and has not recurred.

          -  Patients with simultaneous primaries or bilateral tumors are excluded, with the
             exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0
             differentiated thyroid carcinoma (resected or management deferred), who are eligible.

          -  No prior systemic (chemotherapy or biologic/molecular targeted therapy) or radiation
             treatment for head and neck cancer.

               -  Patients may have received chemotherapy or radiation for a previous, curatively
                  treated non-HNSCC malignancy, provided at least 2 years have elapsed.

               -  Patients must be untreated with radiation above the clavicles.

          -  The patient must consent to a research biopsy at baseline, and during week 2 of
             cisplatin-IMRT.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Age ≥ 18

          -  Patients must have measurable disease according to RECIST 1.1

          -  Patients must demonstrate adequate organ function as defined.

          -  Sexually active patients must agree to use adequate contraceptive measures, while on
             study and for 30 days after the last dose of study drug.

        Exclusion Criteria:

          -  Nasopharyngeal primary site

          -  Current participation in or previous participation in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of study
             treatment.

          -  History of severe allergic or anaphylactic reactions or hypersensitivity to
             recombinant proteins or excipients in the investigational agent.

          -  Distant metastatic disease including CNS or leptomeningeal metastases is not allowed.

          -  History of immunodeficiency or is receiving systemic steroid therapy or any other form
             of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

          -  Received prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
             recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  History of second malignancy within 2 years prior to Study Day 1 (except for excised
             and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial
             bladder cancer, or T1a or T1b prostate cancer comprising < 5% of resected tissue with
             normal prostate specific antigen (PSA) since resection).

          -  Active autoimmune disease requiring systemic treatment within the past 3 months or a
             documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents.

          -  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).

          -  Received a live vaccine within 30 days prior to the first dose of trial treatment.

          -  Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways).

          -  Significant pulmonary disease, including pulmonary hypertension, interstitial lung
             disease, or active, non-infectious pneumonitis.

          -  History or current evidence of any other medical or psychiatric condition, therapy, or
             laboratory abnormality that might confound the results of the trial, interfere with
             the subject's participation for the full duration of the trial, or is not in the best
             interest of the subject to participate, in the opinion of the treating investigator.

          -  Peripheral neuropathy ≥ Grade 2

          -  Significant cardiovascular disease, including:

               -  Cardiac failure New York Heart Association (NYHA) class III or IV.

               -  Myocardial infarction, severe or unstable angina within 6 months prior to Study
                  Day 1.

               -  History of serious arrhythmia (i.e., ventricular tachycardia, or ventricular
                  fibrillation).

               -  Ventricular cardiac arrhythmias requiring anti-arrhythmic medications.

               -  Known left ventricular ejection fraction (LVEF) ≤ 50%.

          -  Significant thrombotic or embolic events within 3 months prior to Study Day 1.

          -  Major surgery within 6 weeks prior to Study Day 1 (subjects must have completely
             recovered from any previous surgery prior to Study Day 1). Biopsy, diagnostic
             tonsillectomy, airway tumor debulking or excisional lymph node biopsy do not
             constitute major surgery.

          -  Active infection requiring antibiotics or antifungals within 7 days prior to first
             dose of study drug.

          -  Significant electrolyte imbalance prior to enrollment (note that patients may be
             supplemented to achieve acceptable electrolyte values):

               -  Hypomagnesemia <1.2 mg/dL or 0.5 mmol/L.

               -  Hypokalemia < 3.0 mmol/L.

          -  Women must not be pregnant or breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:1-year progression-free survival
Time Frame:1 year
Safety Issue:
Description:Progression-free survival as determined by history, clinical examination, radiologic evaluation of tumor response, and pathologic confirmation of recurrence

Secondary Outcome Measures

Measure:PD-L1 expression in paired tumor biopsies
Time Frame:1 month
Safety Issue:
Description:PD-L1 expression will be studied by immunohistochemistry in tumor biopsies obtained at baseline and during week 2 of protocol treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pittsburgh

Trial Keywords

  • Head and Neck
  • Locally Advanced
  • Squamous Cell Carcinoma
  • SCCHN
  • Untreated
  • High Risk
  • Intermediate Risk
  • Radiation Therapy
  • Cisplatin

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