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Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in Combination w/ Tremelimumab Squamous Cell Carcinoma of the Head and Neck

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02319044
First received: December 12, 2014
Last updated: August 8, 2016
Last verified: August 2016
  Purpose
The purpose of this study is to determine the efficacy and safety of investigational medical products (MEDI4736 monotherapy, tremelimumab monotherapy, and MEDI4736 + tremelimumab combination therapy) in the treatment of patients with recurrent or metastatic carcinoma of the head and neck who have progressed during or after treatment with a platinum containing regimen for recurrent/metastatic disease.

Condition Intervention Phase
Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck
Drug: MEDI4736
Drug: Tremelimumab
Drug: MEDI4736 + Tremelimumab
Phase 2

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 II, Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy, Tremelimumab Monotherapy, and MEDI4736 in Combination With Tremelimumab 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:
  • Objective Response Rate (ORR) [ Time Frame: after 12 month ] [ Designated as safety issue: No ]
    the number (%) of patients with a confirmed overall response of CR (complete response) or PR (partial response) and will be based on all treated patients who have measurable disease at baseline per ICR (evaluable set)


Secondary Outcome Measures:
  • Duration of response (DoR) [ Time Frame: after 12 month ] [ Designated as safety issue: No ]
    time from the date of first documented response until the first date of documented progression or death in the absence of disease progression

  • Disease control rate (DCR) [ Time Frame: after 12 month ] [ Designated as safety issue: No ]
    percentage of patients who have a BoR (best objective response) of CR(complete response) or PR (partial response) or who have demonstrated SD (stable disease)

  • Progression-free survival (PFS) [ Time Frame: after 12 month ] [ Designated as safety issue: No ]
    time from the date of randomization until the date of objective disease progression or death

  • Overall survival (OS) [ Time Frame: after 12 month ] [ Designated as safety issue: No ]
    time from the date of randomization until death due to any cause

  • Best objective response (BoR) [ Time Frame: after 12 month ] [ Designated as safety issue: No ]
    the best response a patient has had during their time in the study


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: after 12 month ] [ Designated as safety issue: Yes ]
    the safety and tolerability profile


Estimated Enrollment: 240
Study Start Date: April 2015
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI4736
MEDI4736 monotherapy
Drug: MEDI4736
MEDI4736 monotherapy
Experimental: Tremelimumab
Tremelimumab monotherapy
Drug: Tremelimumab
Tremelimumab monotherapy
Experimental: MEDI4736 + Tremelimumab
MEDI4736 + Tremelimumab combination therapy
Drug: MEDI4736 + Tremelimumab
MEDI4736 + Tremelimumab combination therapy

Detailed Description:

This is a randomized, open-label, multi-center, global, Phase II study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy and tremelimumab monotherapy in the treatment of patients with recurrent or metastatic PD-L1-negative squamous cell carcinoma of the head and neck (SCCHN) who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease, that must have contained a platinum agent.

Patients will be randomized in a stratified manner according to prognostic factors, including human papillomavirus (HPV) status and smoking status to achieve a balance between treatments for each of the factors. Patients will be randomized in a 1:1:2 fashion to receive MEDI4736 monotherapy, tremelimumab monotherapy, or MEDI4736 + tremelimumab combination.

All treatments will be administered beginning on Day 0 for 12 months or until confirmed progression of disease; unless, in the Investigator's opinion, the patient continues to receive benefit from the treatment), initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. Patients with confirmed progression of disease who, in the Investigator's opinion, continue to receive benefit from their assigned investigational product and who meet the criteria for treatment in the setting of progression of disease may continue to receive their assigned investigational product treatment for a maximum of 12 months after consultation with the Sponsor and at the Investigator's discretion. The monotherapy arms (tremelimumab and MEDI4736) should be discontinued if there is confirmed progression of disease following a previous response in target lesions (complete response or partial response).

Tumor assessments will be performed using computed tomography or magnetic resonance imaging. Efficacy for all patients will be assessed by objective tumor assessments every 8 weeks (q8w) for the first 48 weeks (relative to the date of the first infusion) then q12w in patients who have disease control after 12 months until confirmed objective disease progression.

Following completion or discontinuation of treatment, patients will enter a follow-up period.

  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 confirmed recurrent or metastatic SCCHN; tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent; Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible.
  • Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
  • Confirmed PD-L1-negative SCCHN by Ventana SP263;
  • WHO/ECOG performance status of 0 or 1;
  • At least 1 measurable lesion at baseline;
  • No prior exposure to immune-mediated therapy;
  • Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test.

Exclusion Criteria:

  • Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck;
  • Received more than 1 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;
  • another primary malignancy
  • Patients with history of brain metastases, spinal cord compression, or a history of leptomeningeal carcinomatosis;
  • History of active primary immunodeficiency;
  • Known history of previous 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;
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
  • Known allergy or hypersensitivity to Investigational Product.
  • Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results
  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: NCT02319044

  Show 113 Study Locations
Sponsors and Collaborators
AstraZeneca
PRA Health Sciences
Investigators
Study Director: Anthony Jarkowski III Medical Scientist AstraZeneca Anthony.Jarkowski@astrazeneca.com
Principal Investigator: Lillian Siu, MD Princess Margaret Hospital in Toronto, Ontario
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02319044     History of Changes
Other Study ID Numbers: D4193C00003 
Study First Received: December 12, 2014
Last Updated: August 8, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: National Agency for the Safety of Medicine and Health Products
Germany: Paul-Ehrlich-Institute
Hungary: National Institute of Pharmacy
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
United States: Institutional Review Board
Australia: Therapeutic Goods Administration
Georgia: Ministry of Labor, Health and Social affairs of Georgia
Israel: MOH, Pharmaceutical Department, Clinical Trials Unit
Malaysia: National Pharmaceutical Control Bureau
S.Korea: Ministry of Food and Drug Safety
Taiwan: Taiwan Food and Drug Administration

Keywords provided by AstraZeneca:
Head and neck cancer; SCCHN

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 September 28, 2016