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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 : Active, not recruiting
First Posted : September 16, 2015
Last Update Posted : September 7, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

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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
Estimated Study Completion Date : February 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

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




Primary Outcome Measures :
  1. To assess the efficacy of MEDI4736 monotherapy compared to Standard of Care (SoC, EXTREME) in terms of overall survival (OS) [ Time Frame: Estimated up to 2 years ]
    PD-L1 TC/IC high subgroup


Secondary Outcome Measures :
  1. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Overall Survival (OS) [ Time Frame: Estimated up to 2 years ]
    OS in low risk of early mortality (EM) subgroup, ctDNA TMB high subgroup, all-comers and in the PD-L1 TC/IC high subgroup

  2. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Objective Response Rate (ORR) [ Time Frame: Estimated up to 2 years ]
    ORR in the PD-L1 TC/IC high subgroup, low risk of EM subgroup, ctDNA TMB high subgroup and all-comers using investigator assessments according to RECIST 1.1

  3. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Progression Free Survival (PFS) [ Time Frame: Estimated up to 2 years ]
    PFS in the PD-L1 TC/IC high subgroup, low risk of EM subgroup, ctDNA TMB high subgroup and all-comers using investigator assessments according to RECIST 1.1

  4. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Second Progression (PFS2) [ Time Frame: Estimated up to 2 years ]
    PFS2 using local standard clinical practice in the PD-L1 TC/IC high subgroup, and all-comers

  5. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Duration of Response (DoR) [ Time Frame: Estimated up to 2 years ]
    DOR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup and all-comers

  6. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Best Objective Response (BoR) [ Time Frame: Estimated up to 2 years ]
    BoR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup and all-comers.

  7. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Time to Response (TTR) [ Time Frame: Estimated up to 2 years ]
    TTR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup and all-comers.

  8. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Time to First Subsequent Therapy (TFST) [ Time Frame: Estimated up to 2 years ]
    TFST in the PD-L1 TC/IC high subgroup and all-comers

  9. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Time to Second Subsequent Therapy (TSST) [ Time Frame: Estimated up to 2 years ]
    TSST in the PD-L1 TC/IC high subgroup and all-comers

  10. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Overall Survival at 12, 18 and 24 Months (OS12, OS18, OS24) over a period of 2 years [ Time Frame: Estimated up to 2 Years ]
    OS12, OS18 and OS24 in the low risk of EM subgroup, ctDNA TMB high subgroup, all-comers and in the PD-L1 TC/IC high subgroup

  11. The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Alive and Progression Free at 6 and 12 Months (APF6, APF12) over a period of 1 year [ Time Frame: Estimated up to 1 Year ]
    APF6 and APF12 in the PD-L1 TC/IC subgroup, low risk of EM subgroup, ctDNA TMB high subgroup and all-comers using site investigator assessments according to RECIST 1.1

  12. The efficacy of MEDI4736 monotherapy vs SoC in terms of Duration of Response(DoR) [ Time Frame: Estimated up to 2 years ]
    DoR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup and all-comers

  13. The efficacy of MEDI4736 monotherapy vs SoC in terms of Time to Response (TTR) [ Time Frame: Estimated up to 2 years ]
    TTR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup and all-comers

  14. The efficacy of MEDI4736 monotherapy vs SoC in terms of Time to First Subsequent Therapy(TFST) [ Time Frame: Estimated up to 2 years ]
    TFST in the PD-L1 TC/IC high subgroup and all-comers

  15. The efficacy of MEDI4736 monotherapy vs SoC in terms of Time to Second Subsequent Therapy(TSST) [ Time Frame: Estimated up to 2 years ]
    TSST in the PD-L1 TC/IC high subgroup and all-comers

  16. The efficacy of MEDI4736 monotherapy vs SoC in terms of Best Objective Response (BoR) [ Time Frame: Estimated up to 2 Years ]
    BoR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup and all-comers

  17. The efficacy of MEDI4736 monotherapy vs SoC in terms of proportion of patients Alive and Progression Free at 6 and 12 Months (APF6, APF12) over a period of 1 year [ Time Frame: Estimated up to 1 year ]
    APF6 and APF12 using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup, low risk of EM subgroup, ctDNA TMB high subgroup and all-comers

  18. The efficacy of MEDI4736 monotherapy compared to SoC in terms of Progression Free Survival (PFS) and Second Progression (PFS2) [ Time Frame: Estimated up to 2 years ]

    PFS using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup, low risk of EM subgroup, ctDNA TMB high subgroup and all-comers

    PFS2 using local standard clinical practice in the PD-L1 TC/IC high subgroup and all-comers


  19. The efficacy of MEDI4736 monotherapy compared to SoC in terms of Overall Survival (OS) and Overall Survival at 12, 18 and 24 months (OS12, OS18, OS24) [ Time Frame: Estimated up to 2 Years ]

    OS in low risk of EM subgroup, ctDNA TMB high subgroup and all-comers

    OS12, OS18 and OS24 in the low risk of EM subgroup, ctDNA TMB high subgroup all-comers and PD-L1 TC/IC high subgroup


  20. The efficacy of MEDI4736 monotherapy compared to SoC in terms of Objective Response Rate (ORR) [ Time Frame: Estimated up to 2 years ]
    ORR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC high subgroup, low risk of EM subgroup, ctDNA TMB high subgroup and all-comers

  21. The efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Progression Free Survival (PFS) [ Time Frame: Estimated up to 2 years ]
    PFS using site investigator assessments according to RECIST 1.1 in the low risk of EM subgroup, ctDNA TMB high subgroup, PD-L1 TC/IC high subgroup and all-comers

  22. The efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Objective Response Rate (ORR) [ Time Frame: Estimated up to 2 years ]
    ORR using site investigator assessments according to RECIST 1.1 in the low risk of EM subgroup, ctDNA TMB high subgroup, PD-L1 TC/IC high subgroup and all-comers

  23. The efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Overall Survival (OS) [ Time Frame: Estimated up to 2 years ]
    OS in the low risk of EM subgroup, ctDNA TMB high subgroup, PD-L1 TC/IC high subgroup and all-comers

  24. The pharmacokinetics (PK) analysis of MEDI4736 and Tremelimumab using Area Under the Curve (AUC) [ Time Frame: Estimated up to 6 months ]
    After the first and steady-state doses: peak and trough concentrations of MEDI4736 and Tremelimumab will be determined.

  25. The immunogenicity of MEDI4736 and tremelimumab [ Time Frame: Estimated up to 2 years ]
    Serum will be tested for the presence of anti-drug antibodies.

  26. HRQoL in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30) module [ Time Frame: Estimated up to 2 years ]
    EORTC QLQ-C30: global health QoL, functioning (physical) and symptoms (fatigue) in the PD-L1 TC/IC high subgroup and all-comers

  27. HRQoL in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the European Organization for Research and Treatment of Cancer Head and Neck Quality of Life (EORTC QLQ-H&N35) module [ Time Frame: Estimated up to 2 years ]
    EORTC QLQ-H&N35: symptoms (pain, swallowing) in the primary analysis population, and all-comers Changes in WHO/ECOG performance status in the PD-L1 TC/IC high subgroup and all-comers

  28. The pharmacokinetics (PK) analysis of MEDI4736 and Tremelimumab using Maximum Plasma Concentration (Cmax) [ Time Frame: Estimated up to 6 months ]
    After the first and steady-state doses: peak and trough concentrations of MEDI4736 and Tremelimumab will be determined.


Other Outcome Measures:
  1. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-Adverse Events [ Time Frame: Estimated up to 2 years ]
    Adverse Events in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers

  2. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-Physical Examination [ Time Frame: Estimated up to 2 years ]
    Incidence of abnormal physical examination findings in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers

  3. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-Clinical Chemistry [ Time Frame: Estimated up to 2 years ]
    Incidence of abnormal clinical chemistry test results in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers

  4. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-Hematology [ Time Frame: Estimated up to 2 years ]
    Incidence of abnormal hematology test results in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers

  5. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-Urinalysis [ Time Frame: Estimated up to 2 years ]
    Incidence of abnormal urinalysis test results in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers

  6. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-Blood Pressure [ Time Frame: Estimated up to 2 years ]
    Incidence of abnormal vital signs (systolic and diastolic blood pressure) in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers

  7. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-Pulse [ Time Frame: Estimated up to 2 years ]
    Vital signs (pulse) in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers

  8. Safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC (EXTREME) in the first-line setting for treatment of SCCHN-ECG [ Time Frame: Estimated up to 2 years ]
    Incidence of abnormal ECG (QTcF) findings in PD-L1 TC/IC high subgroup, low risk of EM subgroup and all-comers



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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

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
Show Show 196 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
Layout table for investigator information
Study Director: Richard Olsson
Principal Investigator: Tanguy Seiwert The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02551159    
Other Study ID Numbers: D419LC00001
First Posted: September 16, 2015    Key Record Dates
Last Update Posted: September 7, 2020
Last Verified: August 2020

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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