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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03040999




Registration number
NCT03040999
Ethics application status
Date submitted
1/02/2017
Date registered
2/02/2017
Date last updated
26/02/2024

Titles & IDs
Public 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)
Scientific 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)
Secondary ID [1] 0 0
MK-3475-412
Secondary ID [2] 0 0
3475-412
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Cisplatin
Treatment: Other - Accelerated Fractionation (AFX) Radiotherapy
Treatment: Other - Standard Fractionation (SFX) Radiotherapy

Experimental: Pembrolizumab + Cisplatin + CRT - 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 Comparator: Placebo + Cisplatin + CRT - 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.


Other interventions: Pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

Treatment: Drugs: Placebo
Normal saline or dextrose solution administered as an IV infusion Q3W

Treatment: Drugs: Cisplatin
100 mg/m^2 administered as an IV infusion Q3W

Treatment: Other: Accelerated Fractionation (AFX) Radiotherapy
70 Gray (Gy) given in 35 fractions over 6 weeks

Treatment: Other: Standard Fractionation (SFX) Radiotherapy
70 Gy given in 35 fractions over 7 weeks
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS)
Timepoint [1] 0 0
Up to approximately 62 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 62 months
Secondary outcome [2] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [2] 0 0
From time of first dose of study treatment until 90 days after last dose (up to approximately 19 months)
Secondary outcome [3] 0 0
Number of Participants Discontinuing Study Drug Due to an AE
Timepoint [3] 0 0
From time of first dose of study treatment until the end of treatment (up to approximately 16 months)
Secondary outcome [4] 0 0
Change From Baseline in Global Health Status/Quality of Life (GHS/QoL)
Timepoint [4] 0 0
Prior to the first dose of study treatment (Baseline) and up to Week 45
Secondary outcome [5] 0 0
Change From Baseline in Swallowing, Speech, and Pain Symptoms
Timepoint [5] 0 0
Prior to the first dose of study treatment (Baseline) and up to Week 45
Secondary outcome [6] 0 0
Change From Baseline in Physical Functioning
Timepoint [6] 0 0
Prior to the first dose of study treatment (Baseline) and up to Week 45

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
16/08/2024
Actual
Sample size
Target
Accrual to date
Final
804
Recruitment in Australia
Recruitment state(s)
NSW, (Australia)NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital ( Site 0301) - Liverpool
Recruitment hospital [2] 0 0
Blacktown Hospital Western Sydney Local Health District ( Site 0304) - Blacktown
Recruitment hospital [3] 0 0
Princess Alexandra Hospital ( Site 0305) - Brisbane
Recruitment hospital [4] 0 0
Royal Brisbane and Women s Hospital ( Site 0302) - Herston
Recruitment hospital [5] 0 0
Royal Adelaide Hospital ( Site 0303) - Adelaide
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Centre ( Site 0300) - Melbourne
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2148 - Blacktown
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Connecticut
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Illinois
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Indiana
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United States of America
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Louisiana
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United States of America
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Massachusetts
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United States of America
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Michigan
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Missouri
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Montana
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Nevada
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New York
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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Texas
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Virginia
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Washington
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Austria
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Graz
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Austria
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Linz
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Austria
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Salzburg
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Austria
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Vienna/Wien
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Belgium
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Brussels
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liege
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Belgium
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Namur
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Bahia
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Ceara
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Rio Grande Do Norte
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Rio Grande Do Sul
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RS
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Sao Paulo
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Brazil
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SP
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Brazil
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Ribeirao Preto
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Rio de Janeiro
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Canada
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Alberta
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Ontario
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Canada
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Quebec
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Colombia
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Antioquia
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Colombia
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Valle Del Cauca
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Colombia
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Bogota
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Czechia
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Brno
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Czechia
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Hradec Kralove
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Czechia
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Olomouc
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Czechia
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Ostrava
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Czechia
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Praha 8
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Czechia
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Praha
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France
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Le Mans
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France
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Limoges
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France
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Toulouse Cedex 09
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France
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Vandoeuvre les Nancy
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France
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Villejuif
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Germany
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Erlangen
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Germany
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Gera
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Germany
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Hamburg
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Hannover
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Germany
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Luebeck
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Germany
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Munchen
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Germany
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Ulm
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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MO
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Italy
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Firenze
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Milano
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Napoli
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Italy
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Padova
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Italy
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Pavia
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Japan
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Chiba
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Hokkaido
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Japan
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Hyogo
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Kagawa
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Miyagi
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Hiroshima
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Osaka
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Tokyo
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Korea, Republic of
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Chungcheongbuk Do
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Gyeonggi-do
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Korea, Republic of
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Daejeon
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Korea, Republic of
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Seoul
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Netherlands
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Alkmaar
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Amsterdam
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Netherlands
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Groningen
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Netherlands
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Nijmegen
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Netherlands
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Rotterdam
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New Zealand
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Newtown
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Poland
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Dolnoslaskie
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Poland
State/province [91] 0 0
Mazowieckie
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Poland
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Bielsko-Biala
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Poland
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Gdynia
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Poland
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Gliwice
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Poland
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Krakow
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Poland
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Szczecin
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Poland
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Warszawa
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Spain
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Barcelona
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Spain
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Hospitalet de Llobregat
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Valencia
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Turkey
State/province [108] 0 0
Adana
Country [109] 0 0
Turkey
State/province [109] 0 0
Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Kocaeli
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Turkey
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Malatya
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Norfolk
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United Kingdom
State/province [115] 0 0
Staffordshire
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United Kingdom
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Suffolk
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United Kingdom
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London
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United Kingdom
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Preston
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United Kingdom
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Southampton
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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 website
https://clinicaltrials.gov/ct2/show/NCT03040999
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03040999