Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02551159
First received: September 9, 2015
Last updated: November 23, 2016
Last verified: November 2016
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of progression-free survival (PFS). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Overall survival (OS). [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Objective Response Rate (ORR). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Second Progression (PFS2). [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Duration of Response (DoR). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of alive and progression free at 12 months (APF12). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of overall survival at 24 months (OS24). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 monotherapy compared to SoC in terms of progression-free survival (PFS). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 monotherapy compared to SoC in terms of Overall survival (OS). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 monotherapy compared to SoC in terms of Objective Response Rate (ORR). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 monotherapy compared to SoC in terms of Second Progression (PFS2). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The efficacy of MEDI4736 monotherapy compared to SoC in terms of overall survival at 24 months (OS24). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Progression Free Survival (PFS). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Objective Response Rate (ORR). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Overall Survival (OS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The pharmacokinetics (PK) analysis of MEDI4736 and Tremelimumab using Area Under the Curve (AUC) [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    After the first and steady-state doses: peak and trough concentrations of MEDI4736 and Tremelimumab will be determined.

  • The immunogenicity of MEDI4736 and tremelimumab [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Serum will be tested for the presence of anti-drug antibodies.

  • Health related quality of life (HRQoL) in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • HRQoL in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the EORTC- 35-item Head and Neck Quality of Life Questionnaire (QLQ H&N35) module [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • The pharmacokinetics (PK) analysis of MEDI4736 and Tremelimumab using Maximum Plasma Concentration (Cmax) [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    After the first and steady-state doses: peak and trough concentrations of MEDI4736 and Tremelimumab will be determined.


Other Outcome Measures:
  • The safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC will be determined using vital signs, laboratory data, electrocardiograms (ECGs), and physical examination [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 760
Study Start Date: October 2015
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02551159

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 230 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Michael McDevitt 200 Orchard Ridge Drive 1208F, Gaithersburg, MD
Principal Investigator: Tanguy Seiwert The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02551159     History of Changes
Other Study ID Numbers: D419LC00001 
Study First Received: September 9, 2015
Last Updated: November 23, 2016
Health Authority: United States: Food and Drug Administration

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:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Tremelimumab
Carboplatin
Cetuximab
Fluorouracil
Antibodies, Monoclonal
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on January 14, 2017