Clinical trial NCT02551159: Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Squamous Cell Carcinoma of the Head and Neck
Keywords: programmed cell death ligand 1 (PD-L1), MEDI4736, Cytotoxic T-lymphocyte-associated antigen 4 {CTLA-4}, PFS, SCCHN
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-09-16
Enrollment: 823
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)
timeFrame: From date of randomization until time of final analysis, an average of approximately 4 years
measure: Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup
timeFrame: From date of randomization until time of final analysis, an average of approximately 4 years
Secondary outcomes:
measure: Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)
timeFrame: From date of randomization until time of final analysis, an average of approximately 4 years
measure: Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup
timeFrame: 12, 18 and 24 months after randomization
measure: Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup
timeFrame: 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
measure: Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup
timeFrame: 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
measure: Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup
timeFrame: 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
measure: Overall Survival (OS) Status in the All-comers (Full Analysis Set)
timeFrame: From date of randomization until time of final analysis, an average of approximately 4 years
measure: Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)
timeFrame: From date of randomization until time of final analysis, an average of approximately 4 years
measure: Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)
timeFrame: 12, 18 and 24 months after randomization
measure: Progression Free Survival (PFS) in the All-comers (Full Analysis Set)
timeFrame: 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
measure: Objective Response Rate (ORR) in the All-comers (Full Analysis Set)
timeFrame: 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
measure: Duration of Response (DoR) in the All-comers (Full Analysis Set)
timeFrame: 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
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Fort Myers
country: United States
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state: Florida
city: Saint Petersburg
country: United States
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state: Florida
city: Tampa
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city: Chicago
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state: Illinois
city: Baltimore
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state: Maryland
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city: Boston
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state: Massachusetts
city: Morristown
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state: New Jersey
city: New York
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state: New York
city: New York
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state: New York
city: Chapel Hill
country: United States
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state: North Carolina
city: Charlotte
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city: Winston-Salem
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city: Columbus
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state: Tennessee
city: Graz
country: Austria
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city: Innsbruck
country: Austria
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city: Linz
country: Austria
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city: Wien
country: Austria
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city: Brussels
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
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city: Bruxelles
country: Belgium
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city: Leuven
country: Belgium
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city: Namur
country: Belgium
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city: Barretos
country: Brazil
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city: Curitiba
country: Brazil
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city: Florianópolis
country: Brazil
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country: Brazil
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city: Porto Alegre
country: Brazil
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country: Brazil
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country: Brazil
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country: Brazil
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country: Brazil
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city: Calgary
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state: Alberta
city: Winnipeg
country: Canada
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state: Manitoba
city: Moncton
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city: Halifax
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city: London
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city: Montreal
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state: Quebec
city: Bordeaux
country: France
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country: France
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city: Dijon
country: France
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city: Lyon Cedex 08
country: France
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city: Nice
country: France
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city: Poitiers Cedex
country: France
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city: Toulouse Cedex
country: France
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city: Vandoeuvre les Nancy
country: France
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city: Villejuif
country: France
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city: Berlin
country: Germany
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city: Erlangen
country: Germany
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city: Essen
country: Germany
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city: Frankfurt am Main
country: Germany
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country: Germany
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country: Germany
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city: Athens
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country: India
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city: Palermo
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city: Salerno
country: Italy
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city: Siena
country: Italy
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city: Torino
country: Italy
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city: Akashi-shi
country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Isehara-shi
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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country: Korea, Republic of
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city: Suwon-si
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country: Philippines
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country: Philippines
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city: Quezon City
country: Philippines
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city: Białystok
country: Poland
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city: Bielsko-Biała
country: Poland
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city: Gdańsk
country: Poland
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city: Gdynia
country: Poland
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city: Lublin
country: Poland
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city: Poznan
country: Poland
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city: Poznan
country: Poland
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city: Szczecin
country: Poland
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country: Poland
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country: Poland
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city: Suceava
country: Romania
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city: Arkhangelsk
country: Russian Federation
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city: Ekaterinburg
country: Russian Federation
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city: Krasnodar
country: Russian Federation
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city: Moscow
country: Russian Federation
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country: Russian Federation
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city: Omsk
country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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city: Sochi
country: Russian Federation
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city: St.Petersburg
country: Russian Federation
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city: Ufa
country: Russian Federation
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country: Slovakia
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city: Kosice
country: Slovakia
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city: Badajoz
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Jaén
country: Spain
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city: L'Hospitalet de Llobregat
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Marbella
country: Spain
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city: Málaga
country: Spain
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city: Valencia
country: Spain
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city: Zaragoza
country: Spain
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city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Pathumthani
country: Thailand
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kapitanivka Village
country: Ukraine
facility: Research Site
city: Kharkiv Region
country: Ukraine
facility: Research Site
city: Kirovohrad
country: Ukraine
facility: Research Site
city: Kryvyi Rih
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Bebington
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
city: Ha Noi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
Study officials:
name: Richard Olsson
role: STUDY_DIRECTOR
affiliation: The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
name: Tanguy Seiwert
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.