Clinical Trials /

Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)

NCT03040999

Description:

The purpose of this study is to determine the efficacy and safety of pembrolizumab given concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The primary hypothesis is that pembrolizumab in combination with CRT is superior to placebo in combination with CRT with respect to event-free survival (EFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR).

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)
  • Official Title: A Randomized Phase III Study of Pembrolizumab Given Concomitantly With Chemoradiation and as Maintenance Therapy Versus Chemoradiation Alone in Subjects With Locally Advanced Head and Neck Squamous Cell Carcinoma (KEYNOTE-412)

Clinical Trial IDs

  • ORG STUDY ID: 3475-412
  • SECONDARY ID: 2016-003934-25
  • SECONDARY ID: MK-3475-412
  • NCT ID: NCT03040999

Conditions

  • Head and Neck Neoplasms

Interventions

DrugSynonymsArms
PlaceboPlacebo + Cisplatin + CRT
CisplatinPlatinol®, Platinol®-AQPembrolizumab + Cisplatin + CRT

Purpose

The purpose of this study is to determine the efficacy and safety of pembrolizumab given concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The primary hypothesis is that pembrolizumab in combination with CRT is superior to placebo in combination with CRT with respect to event-free survival (EFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR).

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + Cisplatin + CRTExperimentalParticipants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen), followed by two cycles of pembrolizumab and cisplatin (3 cycles total) given during CRT. Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab.
      • Cisplatin
    Placebo + Cisplatin + CRTPlacebo ComparatorParticipants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen), followed by two cycles of placebo and cisplatin (3 cycles total) given during CRT. Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo.
      • Placebo
      • Cisplatin

      Eligibility Criteria

      Inclusion Criteria:

      - Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell carcinoma. Participants with oral cavity tumors need to have unresectable disease.

      - Has provided adequate tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy

      - Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1

      - Is eligible for definitive CRT and not considered for primary surgery based on investigator decision

      - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to receiving the first dose of study therapy

      - Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy

      - Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy

      Exclusion Criteria:

      - Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy

      - Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab

      - Has received a live vaccine within 30 days prior to the first dose of study therapy

      - Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer

      - Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for head and neck cancer under study

      - Has not recovered from major surgery prior to starting study therapy

      - Has known active Hepatitis B or C

      - Has known history of Human Immunodeficiency Virus (HIV)

      - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy

      - Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

      - Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.

      - Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization

      - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis

      - Has had previous allogeneic tissue/solid organ transplant

      - Has active infection requiring systemic therapy

      - Has a history of severe hypersensitivity reaction to pembrolizumab, cisplatin or radiotherapy or their analogs

      - Is pregnant or breast feeding or expecting to conceive or father children throughout the study period and for up to 180 days after the last dose of study therapy

      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:EFS per RECIST Version 1.1 by BICR
      Time Frame:Up to 5 years
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:Overall Survival (OS)
      Time Frame:Up to 5 years
      Safety Issue:
      Description:
      Measure:Number of Participants with Adverse Events (AEs)
      Time Frame:From time of first dose of study treatment until the end of follow-up (up to 5 years)
      Safety Issue:
      Description:
      Measure:Number of Participants Discontinuing Study Treatment Due to AEs
      Time Frame:From time of first dose of study treatment until the end of treatment (up to 1 year)
      Safety Issue:
      Description:
      Measure:Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30)
      Time Frame:Prior to the first dose of study treatment (Baseline) and at the time of last follow-up (up to 5 years)
      Safety Issue:
      Description:
      Measure:Change From Baseline in Swallowing, Speech, and Pain Symptoms Using the EORTC Head and Neck Questionnaire (EORTC QLQ-H&N35)
      Time Frame:Prior to the first dose of study treatment (Baseline) and at the time of last follow-up (up to 5 years)
      Safety Issue:
      Description:

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Merck Sharp & Dohme Corp.

      Trial Keywords

      • Head and Neck Squamous Cell Carcinoma
      • Programmed Cell Death Receptor 1 (PD-1)
      • Programmed Cell Death Receptor Ligand 1 (PD-L1)
      • Programmed Cell Death Receptor Ligand 2 (PD-L2)
      • PD1
      • PD-1
      • PDL1
      • PD-L1
      • PDL2

      Last Updated

      March 20, 2017