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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02551159
Recruitment Status : Completed
First Posted : September 16, 2015
Results First Posted : October 13, 2021
Last Update Posted : October 13, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Head and Neck Biological: MEDI4736 Biological: Tremelimumab Biological: MEDI4736+Tremelimumab Biological: Cetuximab Drug: 5-fluorouracil (5FU) Drug: Cisplatin Drug: Carboplatin Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 823 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 15, 2015
Actual Primary Completion Date : July 6, 2020
Actual Study Completion Date : May 21, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Monotherapy
MEDI4736 monotherapy.
 Biological: MEDI4736
Anti-PD-L1 antibody
Experimental: Combination Therapy
MEDI4736+Tremelimumab combination therapy
 Biological: Tremelimumab
Anti-CTLA-4 Antibody

Biological: MEDI4736+Tremelimumab
Active Comparator: Standard of Care
Standard of Care treatment
 Biological: Cetuximab
Monoclonal Antibody

Drug: 5-fluorouracil (5FU)
Chemotherapy Agent

Drug: Cisplatin
Chemotherapy agent

Drug: Carboplatin
Chemotherapy Agent


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02551159


Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Richard Olsson
Principal Investigator: Tanguy Seiwert The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] June 29, 2020
Statistical Analysis Plan  [PDF] December 16, 2020

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02551159    
Other Study ID Numbers: D419LC00001
First Posted: September 16, 2015    Key Record Dates
Results First Posted: October 13, 2021
Last Update Posted: October 13, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
programmed cell death ligand 1 (PD-L1), MEDI4736, Cytotoxic T-lymphocyte-associated antigen 4 {CTLA-4}, PFS, SCCHN
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carboplatin
Fluorouracil
Cetuximab
 Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological