February 1, 2017
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February 2, 2017
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February 27, 2020
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April 5, 2017
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April 16, 2021 (Final data collection date for primary outcome measure)
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Event-free Survival (EFS) [ Time Frame: Up to 5 years ] EFS is the time from the date of randomization to the date of first record of disease progression or death.
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EFS per RECIST Version 1.1 by BICR [ Time Frame: Up to 5 years ]
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- Overall Survival (OS) [ Time Frame: Up to 5 years ]
OS is the time from randomization to death due to any cause.
- Adverse Events (AEs) [ Time Frame: From time of first dose of study treatment until the end of follow-up (up to 5 years) ]
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
- Treatment Discontinuations Due to AEs [ Time Frame: From time of first dose of study treatment until the end of treatment (up to 1 year) ]
Number of participants discontinuing study drug due to an AE
- 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) ]
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)
- 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) ]
Change from baseline in swallowing, speech, and pain symptoms using the EORTC Head and Neck Questionnaire (EORTC QLQ-H&N35)
- 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) ]
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
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- Overall Survival (OS) [ Time Frame: Up to 5 years ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
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Not Provided
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Not Provided
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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)
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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)
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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).
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Not Provided
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
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Head and Neck Neoplasms
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- Biological: Pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Name: KEYTRUDA®
- Drug: Placebo
Normal saline or dextrose solution administered as an IV infusion Q3W
- Drug: Cisplatin
100 mg/m^2 administered as an IV infusion Q3W
- Radiation: Accelerated Fractionation (AFX) Radiotherapy
70 Gray (Gy) given in 35 fractions over 6 weeks
- Radiation: Standard Fractionation (SFX) Radiotherapy
70 Gy given in 35 fractions over 7 weeks
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- 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.
Interventions:
- Biological: Pembrolizumab
- Drug: Cisplatin
- Radiation: Accelerated Fractionation (AFX) Radiotherapy
- Radiation: Standard Fractionation (SFX) Radiotherapy
- 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.
Interventions:
- Drug: Placebo
- Drug: Cisplatin
- Radiation: Accelerated Fractionation (AFX) Radiotherapy
- Radiation: Standard Fractionation (SFX) Radiotherapy
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Machiels JP, Tao Y, Burtness B, Tahara M, Licitra L, Rischin D, Waldron J, Simon C, Gregoire V, Harrington K, Alves GV, Figueiredo Lima IP, Pointreau Y, M Hughes BG, Aksoy S, Hetnal M, Ge JY, Brown H, Cheng J, Bidadi B, Siu LL. Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Future Oncol. 2020 Jun;16(18):1235-1243. doi: 10.2217/fon-2020-0184. Epub 2020 Jun 3.
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Active, not recruiting
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780
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Same as current
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June 29, 2023
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April 16, 2021 (Final data collection date for primary outcome measure)
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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
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Australia, Austria, Belgium, Brazil, Canada, Colombia, Czechia, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Spain, Taiwan, Turkey, United Kingdom, United States
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Argentina, Chile, Czech Republic, Hungary, Mexico, Puerto Rico, Ukraine
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NCT03040999
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3475-412 2016-003934-25 ( EudraCT Number ) MK-3475-412 ( Other Identifier: Merck ) 173640 ( Registry Identifier: JAPIC-CTI ) KEYNOTE-412 ( Other Identifier: Merck )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
URL: |
http://engagezone.msd.com/ds_documentation.php |
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Merck Sharp & Dohme Corp.
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Merck Sharp & Dohme Corp.
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Not Provided
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Study Director: |
Medical Director |
Merck Sharp & Dohme Corp. |
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Merck Sharp & Dohme Corp.
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February 2020
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