Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

— KESTREL  

Official title:

A Phase III Randomized, Open-label, Multi-center, Global Study of MEDI4736 Alone or in Combination With Tremelimumab Versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02551159
• Other study ID #: D419LC00001
• Status: Completed
• Phase: Phase 3
• Start date: October 15, 2015
• Est. completion date: May 21, 2021

Study information

• Verified date: September 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Patients will be randomized in a 2:1:1 ratio to MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or SoC. Patients in all arms will continue therapy until progression. Tumor assessments will be performed on computed tomography scans or magnetic resonance imaging scans, preferably with intravenous (IV) contrast. Efficacy for all patients will be assessed by objective tumor assessments every 6 weeks for the first 24 weeks, then every 8 weeks thereafter until treatment discontinuation due to progression or toxicity. All patients will be followed every 3 months for survival after progression is confirmed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 823
• Est. completion date: May 21, 2021
• Est. primary completion date: July 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Age =18 years at the time of screening

2. Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx).

3. 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.

4. No prior systemic chemotherapy for recurrent or metastatic disease

5. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment

6. No prior exposure to immune-mediated therapy,

Exclusion Criteria:

1. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland)

2. Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting

3. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment

4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis

Related Conditions & MeSH terms

• Head and Neck Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Biological:
• MEDI4736
Anti-PD-L1 antibody
• Tremelimumab
Anti-CTLA-4 Antibody
• MEDI4736+Tremelimumab

• Cetuximab
Monoclonal Antibody

Drug:
• 5-fluorouracil (5FU)
Chemotherapy Agent
• Cisplatin
Chemotherapy agent
• Carboplatin
Chemotherapy Agent

Locations

Country	Name	City	State
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Wien
Belgium	Research Site	Brussels
Belgium	Research Site	Brussels
Belgium	Research Site	Bruxelles
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
Brazil	Research Site	Barretos
Brazil	Research Site	Curitiba
Brazil	Research Site	Florianópolis
Brazil	Research Site	Ijui
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo Andre
Brazil	Research Site	Santo André
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	São Paulo
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Winnipeg	Manitoba
France	Research Site	Bordeaux
France	Research Site	Brest
France	Research Site	Dijon
France	Research Site	Lyon Cedex 08
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Poitiers Cedex
France	Research Site	Toulouse Cedex
France	Research Site	Vandoeuvre les Nancy
France	Research Site	Villejuif
Germany	Research Site	Berlin
Germany	Research Site	Erlangen
Germany	Research Site	Essen
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Freiburg
Germany	Research Site	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Mainz
Germany	Research Site	Tübingen
Germany	Research Site	Würzburg
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Heraklion
Greece	Research Site	Thessaloniki
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Bengaluru
India	Research Site	Gurgaon
India	Research Site	Karamsad
India	Research Site	Madurai
India	Research Site	Pune
Italy	Research Site	Cona
Italy	Research Site	Firenze
Italy	Research Site	Messina
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Palermo
Italy	Research Site	Salerno
Italy	Research Site	Siena
Italy	Research Site	Torino
Japan	Research Site	Akashi-shi
Japan	Research Site	Chiba-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hirakata-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Kobe-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Natori-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama
Japan	Research Site	Sapporo
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Takatsuki-shi
Japan	Research Site	Toyoake-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Hwasun-gun
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seo-Gu
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Philippines	Research Site	Cebu City
Philippines	Research Site	Las Pinas
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Bielsko-Biala
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Romania	Research Site	Suceava
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Sochi
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Ufa
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
Spain	Research Site	Badajoz
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Jaén
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Marbella
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Pathumthani
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kapitanivka Village
Ukraine	Research Site	Kharkiv Region
Ukraine	Research Site	Kirovohrad
Ukraine	Research Site	Kryvyi Rih
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Sumy
Ukraine	Research Site	Vinnytsia
United Kingdom	Research Site	Bebington
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Sutton
United Kingdom	Research Site	Taunton
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Fort Myers	Florida
United States	Research Site	Morristown	New Jersey
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Washington	District of Columbia
United States	Research Site	Winston-Salem	North Carolina
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Austria,  Belgium,  Brazil,  Canada,  France,  Germany,  Greece,  India,  Italy,  Japan,  Korea, Republic of,  Philippines,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab 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
Secondary	Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup	Percentage of patients alive	12, 18 and 24 months after randomization
Secondary	Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup	Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as =20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	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
Secondary	Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup	Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: >= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR)	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
Secondary	Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup	Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression	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
Secondary	Overall Survival (OS) Status in the All-comers (Full Analysis Set)	Number of participants with Overall Survival (OS)	From date of randomization until time of final analysis, an average of approximately 4 years
Secondary	Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)	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	Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)	Percentage of patients alive	12, 18 and 24 months after randomization
Secondary	Progression Free Survival (PFS) in the All-comers (Full Analysis Set)	Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression).; Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as =20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	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
Secondary	Objective Response Rate (ORR) in the All-comers (Full Analysis Set)	Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: >= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR)	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
Secondary	Duration of Response (DoR) in the All-comers (Full Analysis Set)	Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression	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

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