NCT02551159

Brief Summary

This is a randomized, open-label, multi-center, 3-arm, global Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination or MEDI4736 monotherapy versus SoC (EXTREME regimen) in the treatment of patients with SCCHN who have not received prior systemic chemotherapy for recurrent or metastatic disease.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
823

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Oct 2015

Longer than P75 for phase_3

Geographic Reach
23 countries

197 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 9, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 16, 2015

Completed
29 days until next milestone

Study Start

First participant enrolled

October 15, 2015

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 6, 2020

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 21, 2021

Completed
5 months until next milestone

Results Posted

Study results publicly available

October 13, 2021

Completed
Last Updated

October 13, 2021

Status Verified

September 1, 2021

Enrollment Period

4.7 years

First QC Date

September 9, 2015

Results QC Date

July 5, 2021

Last Update Submit

September 16, 2021

Conditions

Keywords

programmed cell death ligand 1 (PD-L1), MEDI4736, Cytotoxic T-lymphocyte-associated antigen 4 {CTLA-4}, PFS, SCCHN

Outcome Measures

Primary Outcomes (2)

  • Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)

    Number of participants with Overall Survival (OS)

    From date of randomization until time of final analysis, an average of approximately 4 years

  • Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup

    Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)

    From date of randomization until time of final analysis, an average of approximately 4 years

Secondary Outcomes (11)

  • Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)

    From date of randomization until time of final analysis, an average of approximately 4 years

  • Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup

    12, 18 and 24 months after randomization

  • Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup

    Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

  • Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup

    Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

  • Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup

    Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

  • +6 more secondary outcomes

Study Arms (3)

Monotherapy

EXPERIMENTAL

MEDI4736 monotherapy.

Biological: MEDI4736

Combination Therapy

EXPERIMENTAL

MEDI4736+Tremelimumab combination therapy

Biological: TremelimumabBiological: MEDI4736+Tremelimumab

Standard of Care

ACTIVE COMPARATOR

Standard of Care treatment

Biological: CetuximabDrug: 5-fluorouracil (5FU)Drug: CisplatinDrug: Carboplatin

Interventions

MEDI4736BIOLOGICAL

Anti-PD-L1 antibody

Monotherapy
TremelimumabBIOLOGICAL

Anti-CTLA-4 Antibody

Combination Therapy
Combination Therapy
CetuximabBIOLOGICAL

Monoclonal Antibody

Standard of Care

Chemotherapy Agent

Standard of Care

Chemotherapy agent

Standard of Care

Chemotherapy Agent

Standard of Care

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years at the time of screening
  • Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx).
  • A fresh tumor biopsy for the purpose of screening or an available archival tumor sample. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy.
  • No prior systemic chemotherapy for recurrent or metastatic disease
  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
  • No prior exposure to immune-mediated therapy,

You may not qualify if:

  • Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting
  • Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis, Crohn's disease\], diverticulitis

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (197)

Research Site

Aurora, Colorado, 80045, United States

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Washington D.C., District of Columbia, 20007, United States

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Fort Myers, Florida, 33916, United States

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St. Petersburg, Florida, 33705, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60637, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21231, United States

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Boston, Massachusetts, 02215, United States

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Morristown, New Jersey, 07960, United States

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New York, New York, 10029, United States

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New York, New York, 10065, United States

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Chapel Hill, North Carolina, 27599, United States

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Charlotte, North Carolina, 28204, United States

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Winston-Salem, North Carolina, 27157, United States

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Cleveland, Ohio, 44115, United States

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Columbus, Ohio, 43210, United States

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Nashville, Tennessee, 37203, United States

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Linz, 4010, Austria

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Vienna, 1140, Austria

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Brussels, 1000, Belgium

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Brussels, 1090, Belgium

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Brussels, 1200, Belgium

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Leuven, 3000, Belgium

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Namur, 5000, Belgium

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Barretos, 14784-400, Brazil

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Curitiba, 81520-060, Brazil

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Florianópolis, 88034-000, Brazil

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Ijuí, 98700-000, Brazil

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Porto Alegre, 90035-003, Brazil

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Porto Alegre, 90619-900, Brazil

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Porto Alegre, 91350-200, Brazil

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Recife, 50040-000, Brazil

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Rio de Janeiro, 22793-080, Brazil

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Santo André, 09060-650, Brazil

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Santo André, 09080-110, Brazil

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São José do Rio Preto, 15090-000, Brazil

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São Paulo, 03102-002, Brazil

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Calgary, Alberta, T2N 4N2, Canada

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Winnipeg, Manitoba, R3E 0V9, Canada

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Moncton, New Brunswick, E1C 8X3, Canada

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Halifax, Nova Scotia, B3H 1V7, Canada

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Hamilton, Ontario, L8V 5C2, Canada

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London, Ontario, N6A 4L6, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Bordeaux, 33000, France

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Brest, 29200, France

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Dijon, 21079, France

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Lyon, 69373, France

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Nice, 06100, France

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Paris, 75015, France

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Poitiers, 86021, France

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Toulouse, 31059, France

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Vandœuvre-lès-Nancy, 54519, France

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Villejuif, 94800, France

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Berlin, 12203, Germany

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Erlangen, 91054, Germany

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Essen, 45147, Germany

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Frankfurt am Main, 60590, Germany

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Freiburg im Breisgau, 79106, Germany

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Hamburg, 20246, Germany

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Heidelberg, 69120, Germany

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Mainz, 55131, Germany

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Tübingen, 72076, Germany

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Würzburg, 97070, Germany

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Athens, 115 22, Greece

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Athens, 11527, Greece

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Athens, 124 61, Greece

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Athens, 18547, Greece

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Heraklion, 711 11, Greece

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Thessaloniki, 54645, Greece

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Bangalore, 560027, India

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Bangalore, 560076, India

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Bengaluru, 560076, India

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Gūrgaon, 122001, India

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Karamsad, 388325, India

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Madurai, 625107, India

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Pune, 411001, India

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Cona, 44124, Italy

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Florence, 50134, Italy

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Messina, 98158, Italy

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Milan, 20133, Italy

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Padua, 35128, Italy

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Palermo, 90127, Italy

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Salerno, 84131, Italy

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Siena, 53100, Italy

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Torino, 10126, Italy

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Akashi-shi, 673-8558, Japan

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Chiba, 260-8717, Japan

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Fukuoka, 811-1347, Japan

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Hirakata-shi, 573-1191, Japan

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Isehara-shi, 259-1193, Japan

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Kagoshima, 890-8520, Japan

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Kanazawa, 920-8650, Japan

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Kitaadachi-gun, 362-0806, Japan

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Kobe, 650-0017, Japan

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Kōtoku, 135-8550, Japan

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Natori-shi, 981-1293, Japan

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Okayama, 700-8558, Japan

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Osaka, 541-8567, Japan

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Sapporo, 003-0804, Japan

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Sapporo, 060-8648, Japan

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Sayama, 589-8511, Japan

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Sunto-gun, 411-8777, Japan

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Takatsuki-shi, 569-8686, Japan

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Toyoake-shi, 470-1192, Japan

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Yokohama, 241-8515, Japan

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Cebu City, 6000, Philippines

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Las Piñas, 1740, Philippines

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Quezon City, 1112, Philippines

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Bialystok, 15-027, Poland

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Bielsko-Biala, 43-300, Poland

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Gdansk, 80-214, Poland

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Gdynia, 81-519, Poland

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Lodz, 93-513, Poland

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Lublin, 20-090, Poland

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Poznan, 60-780, Poland

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Poznan, 61-866, Poland

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Szczecin, 71-730, Poland

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Warsaw, 02-781, Poland

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Suceava, 720237, Romania

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Arkhangelsk, 163045, Russia

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Krasnodar, 350040, Russia

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Moscow, 125367, Russia

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Obninsk, 249036, Russia

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Omsk, 644013, Russia

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Saint Petersburg, 191014, Russia

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Saint Petersburg, 195271, Russia

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Saint Petersburg, 197758, Russia

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Saint Petersburg, 198255, Russia

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Sochi, 354057, Russia

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Ufa, 450054, Russia

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Yekaterinburg, 620905, Russia

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Bratislava, 833 01, Slovakia

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Košice, 041 91, Slovakia

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Cheongju-si, 28644, South Korea

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Hwasun-gun, 58128, South Korea

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Incheon, 21565, South Korea

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Seogu, 49241, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 135-710, South Korea

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Suwon, 16499, South Korea

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Badajoz, 06008, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Jaén, 23007, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Madrid, 28050, Spain

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Marbella, 29600, Spain

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Málaga, 29010, Spain

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Valencia, 46026, Spain

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Zaragoza, 50009, Spain

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Kaohsiung City, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 704, Taiwan

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Taipei, 100, Taiwan

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Taipei, 10449, Taiwan

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Taipei, 11217, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Hat Yai, 90110, Thailand

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Pathum Thani, 12120, Thailand

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Dnipro, 49102, Ukraine

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Ivano-Frankivsk, 76018, Ukraine

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Kapitanivka Village, 08111, Ukraine

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Kharkiv Region, 61070, Ukraine

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Kirovohrad, 25006, Ukraine

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Kryvyi Rih, 50048, Ukraine

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Kyiv, 03022, Ukraine

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Kyiv, 03115, Ukraine

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Odesa, 65055, Ukraine

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Sumy, 40022, Ukraine

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Vinnytsia, 21029, Ukraine

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Bebington, CH63 4JY, United Kingdom

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Birmingham, B15 2TT, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, SW3 6JJ, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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Taunton, TA1 5DA, United Kingdom

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Hanoi, 100000, Vietnam

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Hanoi, Vietnam

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Hà Nội, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Related Publications (2)

  • Seiwert TY, Wildsmith S, Fayette J, Harrington K, Gillison M, Ahn MJ, Takahashi S, Weiss J, Machiels JP, Baxi S, Baker V, Evans B, Morsli N, Jill Walker, Real K, L'Hernault A, Psyrri A. Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2024 Mar 2;73(4):70. doi: 10.1007/s00262-024-03643-3.

  • Hwang M, Seiwert TY. Are taxanes the future for head and neck cancer? Pragmatism in the immunotherapy era. Lancet Oncol. 2021 Apr;22(4):413-415. doi: 10.1016/S1470-2045(21)00121-2. Epub 2021 Mar 5. No abstract available.

Related Links

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

durvalumabtremelimumabCetuximabFluorouracilCisplatinCarboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsHead and Neck NeoplasmsNeoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic Chemicals

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca Clinical Study Information Center

Study Officials

  • Richard Olsson

    STUDY DIRECTOR
  • Tanguy Seiwert

    The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 9, 2015

First Posted

September 16, 2015

Study Start

October 15, 2015

Primary Completion

July 6, 2020

Study Completion

May 21, 2021

Last Updated

October 13, 2021

Results First Posted

October 13, 2021

Record last verified: 2021-09

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
More information

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