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Completed

NCT Number: NCT02551159

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

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.

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Key information

Conditions

Squamous Cell Carcinoma of the Head and Neck Carcinoma Carcinoma, Squamous Cell Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Squamous Cell Carcinoma of Head and Neck

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Graz, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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,

Exclusion criteria

  • 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)
  • 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

Treatment and study plan

MEDI4736

Biological

Anti-PD-L1 antibody

Tremelimumab

Biological

Anti-CTLA-4 Antibody

MEDI4736+tremelimumab

Biological

Cetuximab

Biological

Monoclonal Antibody

5-fluorouracil (5FU)

Drug

Chemotherapy Agent

Cisplatin

Drug

Chemotherapy agent

carboplatin

Drug

Chemotherapy Agent

Primary outcomes

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

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

    Number of participants with Overall Survival (OS)

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

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

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

Secondary outcomes

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

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

    Number of participants with Overall Survival (OS)

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

    Time frame: 12, 18 and 24 months after randomization

    Percentage of patients alive

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

    Time frame: 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

    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

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

    Time frame: 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

    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)

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

    Time frame: 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

    Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression

  6. Overall Survival (OS) Status in the All-comers (Full Analysis Set)

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

    Number of participants with Overall Survival (OS)

  7. Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)

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

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

  8. Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)

    Time frame: 12, 18 and 24 months after randomization

    Percentage of patients alive

  9. Progression Free Survival (PFS) in the All-comers (Full Analysis Set)

    Time frame: 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

    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

  10. Objective Response Rate (ORR) in the All-comers (Full Analysis Set)

    Time frame: 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

    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)

  11. Duration of Response (DoR) in the All-comers (Full Analysis Set)

    Time frame: 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

    Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Acronym: KESTREL

Important dates

Study start
2015
Primary completion
2020
Study completion
2021
First posted
Sep 16, 2015
Registry last updated
Oct 13, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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