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).
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
- SECONDARY ID:
173640
- SECONDARY ID:
KEYNOTE-412
- NCT ID:
NCT03040999
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab | KEYTRUDA® | Pembrolizumab + Cisplatin + CRT |
Placebo | | Placebo + Cisplatin + CRT |
Cisplatin | Platinol®, Platinol®-AQ | Pembrolizumab + 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).
Trial Arms
Name | Type | Description | Interventions |
---|
Pembrolizumab + Cisplatin + CRT | Experimental | Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab. | |
Placebo + Cisplatin + CRT | Placebo Comparator | Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo. | |
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.
Participants with multiple synchronous tumors are not eligible for the study.
- Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker
analysis from a core or excisional biopsy. If an excisional or incisional biopsy has
been performed, participants remain eligible for the study provided the residual
disease meets the staging criteria required for the trial (e.g., excisional biopsy of
a lymph node with residual T4 primary). Prior surgical debulking, including
tonsillectomy, for the head and neck cancer under study is not allowed.
- 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: | Event-free Survival (EFS) |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | EFS is the time from the date of randomization to the date of first record of disease progression or death. |
Secondary Outcome Measures
Measure: | Overall Survival (OS) |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | OS is the time from randomization to death due to any cause. |
Measure: | 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: | Number of participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy |
Measure: | Treatment Discontinuations 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: | Number of participants discontinuing study drug due to an AE |
Measure: | Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) |
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: | Change from baseline in GHS/QoL using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) |
Measure: | Change From Baseline in Swallowing, Speech, and Pain Symptoms |
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: | Change from baseline in swallowing, speech, and pain symptoms using the EORTC Head and Neck Questionnaire (EORTC QLQ-H&N35) |
Measure: | Change From Baseline in Physical Functioning |
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: | Change From Baseline in Physical Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1- 5 Score |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not 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
February 27, 2020