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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02369874
First received: February 18, 2015
Last updated: July 26, 2016
Last verified: July 2016
  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
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 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 ] [ Designated as safety issue: Yes ]
    To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus standard of care in terms of OS


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

  • Overall survival (OS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    To further assess the efficacy of MEDI4736 monotherapy versus standard of care in terms of OS in all patients, regardless of PD-L1 status

  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    The OS24 is defined as the Kaplan-Meier estimate of OS at 24 months.


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 ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability profile


Estimated Enrollment: 720
Study Start Date: September 2015
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 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 objective of the study is 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.

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 for the first 48 weeks and then every 12 weeks as indicated in the schedule of procedures, with categorization of 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)
Genders Eligible for Study:   Both
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 completion of platinum containing 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 210 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: July 26, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Belgium: Federal Agency for Medicinal Products and Health Products
Croatia: Ministry of Health (Ministarstvo zdravlja)
Czech Republic: State Institute for Drug Control
France: National Agency for the Safety of Medicine and Health Products
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Serbia: Medicines and Medical Devices Agency of Serbia
Spain: Spanish Agency of Medicines
Bulgaria: Bulgarian Drug Agency
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Russia: Ministry of Health of the Russian Federation
Chile: Instituto de Salud Pública de Chile
Brazil: National Health Surveillance Agency
Israel: Ethics Commission
Australia: Department of Health and Ageing Therapeutic Goods Administration
Peru: Instituto Nacional de Salud
Japan: Ministry of Health, Labor and Welfare
South Korea: Ministry of Food and Drug Safety
Taiwan:Taiwan Food and Drug Administration, Ministry of Health and Welfare
Ukraine: The State Expert Center of the MOH of Ukraine

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
Antibodies, Monoclonal
Tremelimumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2016