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JOURNAL ONKOLOGIE – STUDIE

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)

Rekrutierend

NCT-Nummer:
NCT03040999

Studienbeginn:
April 2017

Letztes Update:
15.03.2019

Wirkstoff:
Placebo, Cisplatin, Pembrolizumab

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations (3 von 151)

Universitaetsklinikum Schleswig-Holstein-Campus Luebeck ( Site 0803)
23538 Luebeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +4945150042000
» Ansprechpartner anzeigen
UCLA Medical Center ( Site 0273)
90095 Los Angeles
United StatesAktiv, nicht rekrutierend» Google-Maps
Indiana University ( Site 0264)
46202 Indianapolis
United StatesAbgeschlossen» Google-Maps
Oncology Hematology Care, Inc. ( Site 8003)
45242 Cincinnati
United StatesAbgeschlossen» Google-Maps
Medical Oncology Associates (Summit Cancer Centers) ( Site 0257)
99208 Spokane
United StatesAbgeschlossen» Google-Maps
Liverpool Hospital ( Site 0301)
2170 Liverpool
AustraliaAbgeschlossen» Google-Maps
C.H.U. Sart Tilman-Service d'Oncologie Medicale ( Site 0654)
4000 Liege
BelgiumAbgeschlossen» Google-Maps
Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0006)
40050-410 Salvador
BrazilAktiv, nicht rekrutierend» Google-Maps
Juravinski Cancer Centre ( Site 0062)
L8V 5C2 Hamilton
CanadaAbgeschlossen» Google-Maps
London Health Sciences Centre ( Site 0055)
N6A 4L6 London
CanadaAbgeschlossen» Google-Maps
Mazowiecki Szpital Onkologiczny ( Site 1015)
05-135 Wieliszew
PolandAbgeschlossen» Google-Maps
Kocaeli Universitesi Tip Fakultesi ( Site 1106)
41380 Kocaeli
TurkeyAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

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) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR).

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. 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 per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) or death.



Secondary outcome:

1. Overall Survival (OS) (Time Frame - Up to 5 years):
OS is the time from randomization to death due to any cause.

2. 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

3. 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

4. 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)

5. 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)

Studien-Arme

  • 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.

Geprüfte Regime

  • Pembrolizumab (KEYTRUDA®):
    Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
  • Placebo:
    Normal saline or dextrose solution administered as an IV infusion Q3W
  • Cisplatin (Platinol® / Platinol®-AQ / ):
    100 mg/m^2 administered as an IV infusion Q3W
  • Accelerated Fractionation (AFX) Radiotherapy:
    70 Gray (Gy) given in 35 fractions over 6 weeks
  • Standard Fractionation (SFX) Radiotherapy:
    70 Gy given in 35 fractions over 7 weeks

Quelle: ClinicalTrials.gov


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