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Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer (EAGLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02369874
First received: February 18, 2015
Last updated: February 21, 2017
Last verified: February 2017
  Purpose
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.

Condition Intervention Phase
Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Drug: MEDI4736
Drug: MEDI4736 + Tremelimumab
Drug: Standard of Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy and MEDI4736 in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus standard of care in terms of OS

  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    To further assess the efficacy of MEDI4736 + tremelimumab combination therapy versus standard of care in terms of OS in PD-L1 negative patients

  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    To assess the efficacy of MEDI4736 monotherapy versus standard of care in terms of OS in PD-L1 positive patients

  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    To further assess the efficacy of MEDI4736 + tremelimumab combination and MEDI4736 monotherapy versus standard of care in terms of PFS

  • Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    To further assess the efficacy of MEDI4736 + tremelimumab combination and MEDI4736 monotherapy versus standard of care in terms of ORR

  • Duration of response (DoR) [ Time Frame: Up to 2 years ]
    To further assess the efficacy of MEDI4736 + tremelimumab combination and MEDI4736 monotherapy versus standard of care in terms of DoR

  • Disease control rate (DCR) [ Time Frame: Up to 2 years ]
    To further assess the efficacy of MEDI4736 + tremelimumab combination and MEDI4736 monotherapy versus standard of care in terms of DCR

  • Proportion of patients alive and progression free at 6 months (APF6) using investigational site assessments according to RECIST 1.1 [ Time Frame: Up to 2 years ]
    APF6 is defined as the number (%) of patients who are alive and progression free per RECIST 1.1 at 6 months after randomization per Kaplan-Meier estimate of progression free survival at 6 months.

  • Proportion of patients alive and progression free at 12 months (APF12) using investigational site assessments according to RECIST 1.1 [ Time Frame: Up to 2 years ]
    APF12 is defined as the number (%) of patients who are alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of progression free survival at 12 months.

  • Proportion of patients alive at 12 months (OS12) [ Time Frame: up to 2 years ]
    The OS12 is defined as the Kaplan-Meier estimate of OS at 12 months.

  • Proportion of patients alive at 18 months (OS18) [ Time Frame: up to 2 years ]
    The OS18 is defined as the Kaplan-Meier estimate of OS at 18 months.

  • Proportion of patients alive at 24 months (OS24) [ Time Frame: up to 2 years ]
    The OS24 is defined as the Kaplan-Meier estimate of OS at 24 months.

  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of OS in PD-L1-negative patients

  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of PFS in PD-L1-negative patients

  • Overall Response Rate ORR) [ Time Frame: Up to 2 years ]
    To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of ORR in PD-L1-negative patients


Other Outcome Measures:
  • AEs, physical examinations, laboratory findings (including clinical chemistry, hematology, and urinalysis), vital signs (including blood pressure, pulse, and oxygen saturation), and ECGs [ Time Frame: Up to 2 years ]
    To assess the safety and tolerability profile


Estimated Enrollment: 720
Study Start Date: September 2015
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI4736
MEDI4736 monotherapy
Drug: MEDI4736
MEDI4736 Monotherapy
Experimental: MEDI4736 + Tremelimumab
MEDI4736 + tremelimumab combination therapy
Drug: MEDI4736 + Tremelimumab
MEDI4736 + Tremelimumab combination therapy
Active Comparator: Standard of Care
Standard of Care
Drug: Standard of Care
Standard of Care

Detailed Description:

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.

The main objectives of the study are to:

  • assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in patients with squamous cell carcinoma of the head and neck (SCCHN), in terms of overall survival (OS), regardless of PDL-1 status
  • assess the efficacy of MEDI4736 monotherapy versus SOC in patients with SCCHN, in terms of OS, regardless of PDL-1 status

Patients will undergo a screening assessment on their tumor tissue sample to determine PD-L1 expression per a pre-specified cut-off level. Patients with ≥25% of tumor cells with membrane staining will be considered PD-L1 positive while those with 0% to 24% of tumor cells with membrane staining will be considered PD-L1 negative. Based on the underlying PD-L1 status, patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 monotherapy, MEDI4736 + tremelimumab combination therapy, or SoC therapy. Patients who discontinue treatment in 1 treatment group may not switch to treatment in a different group.

Stratification factors include PD-L1 status, human papillomavirus status, (in patients with oropharyngeal cancer only), and smoking status.

Tumor assessments will be performed every 8 weeks until objective tumor response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  Eligibility

Ages Eligible for Study:   18 Years to 96 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
Inclusion Criteria: - Age ≥18 years; - Written informed consent obtained from the patient/legal representative; - Histologically or cytologically confirmed recurrent or metastatic SCCHN; - Tumor progression or recurrence during or after only one palliative systemic treatment regimen for recurrent or metastatic disease that must have contained a platinum agent OR progression within 6 months of the last dose of platinum given as part of multimodality therapy with curative intent; - Confirmed PD-L1-positive or -negative SCCHN by the Ventana PD-L1 SP263 IHC assay; - WHO/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; At least 1 measurable lesion, - Not previously irradiated; - No prior exposure to immune-mediated therapy; - Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Exclusion Criteria: - Histologically or cytologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck; - Received more than 1 palliative systemic regimen for recurrent or metastatic disease; -Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment; - Receipt of any investigational anticancer therapy within 28 days or 5 half-lives; - Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment; - Major surgical procedure within 28 days prior to the first dose of Investigational Product; - Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion; - Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned Investigational Product; - History of allogeneic organ transplantation; - Active or prior documented autoimmune or inflammatory disorders; - Uncontrolled intercurrent illness; - Patients with a history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis; - Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction; - History of active primary immunodeficiency; - Active tuberculosis; - Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV); - Receipt of live, attenuated vaccine within 30 days prior to the first dose of Investigational Product; - Pregnant or breast-feeding female patients; - Known allergy or hypersensitivity to Investigational Product
  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: NCT02369874

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Center Study Locator 1-877-400-4656 astrazeneca@emergingmed.com

  Show 212 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Trishna Goswami, MD Medical Director AstraZeneca
  More Information

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02369874     History of Changes
Other Study ID Numbers: D4193C00002 
Study First Received: February 18, 2015
Last Updated: February 21, 2017

Keywords provided by AstraZeneca:
Head and Neck cancer; MEDI4736; Tremelimumab

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 24, 2017