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Safety and Efficacy of MEDI0457 and Durvalumab in Patients With HPV Associated Recurrent/Metastatic Head and Neck Cancer

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: NCT03162224
Recruitment Status : Active, not recruiting
First Posted : May 22, 2017
Last Update Posted : May 6, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE May 15, 2017
First Posted Date  ICMJE May 22, 2017
Last Update Posted Date May 6, 2020
Actual Study Start Date  ICMJE June 26, 2017
Estimated Primary Completion Date March 19, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2017)
  • Number of patients with changes in electrocariogram (ECG) from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Occurrence of serious adverse events (SAEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of serious adverse events (SAEs)
  • World Health organization (WHO)/ Eastern Cooperative Oncology Group Performace (ECOG) status [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess based on the following: fully active, restricted in physical activity, ambulatory and capable of self care, capable of limited self-care, completely disable.
  • Concomitant medications [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess based on any accompanying or associated medication or procedure
  • Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Number of patients with changes in physical exam from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Number of patients with changes in vital signs from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Occurrence of adverse events (AEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of adverse events (AEs)
  • Objective response Rate (ORR) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess the antitumor activity of MEDI0457 plus Durvalumab in response-evaluable patients
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2017)
  • Number of patients with changes in electrocariogram (ECG) from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Occurrence of serious adverse events (SAEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of serious adverse events (SAEs)
  • World Health organization (WHO)/ Eastern Cooperative Oncology Group Performace (ECOG) status [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess based on the following: fully active, restricted in physical activity, ambulatory and capable of self care, capable of limited self-care, completely disable.
  • Concomitant medications [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess based on any accompanying or associated medication or procedure
  • Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Number of patients with changes in physical exam from baseline [ Time Frame: From time of informed and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Number of patients with changes in vital signs from baseline [ Time Frame: From time of informed and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab
  • Occurrence of adverse events (AEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of adverse events (AEs)
  • Objective response Rate (ORR) [ Time Frame: From time First dose of study medication through 5 years ]
    To assess the antitumor activity of MEDI0457 plus Durvalumab in response-evaluable patients
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2017)
  • Number of subjects who develop anti-drug antibodies [ Time Frame: From time of informed consent through 28 days post end of treatment ]
    To assess the immunogenicity of MEDI0457 and Durvalumab
  • Objective Response Rate (ORR) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab in as-treated patients
  • Progression Free Survival (PFS) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab
  • Disease control Rate (16Weeks) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess anti-tumor activity in MEDI0457 plus Durvalumab
  • Overall Survival (OS) [ Time Frame: From time of first dose of of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab
  • Durva serum cTrough concentration for Pharmacokinetics [ Time Frame: From time of informed consent through 28 days post end of treatment ]
    To assess the pharmacokinetics of Durvalumab
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2017)
  • Number of subjects who develop anti-drug antibodies [ Time Frame: From time of informed consent through 28 days post end of treatment ]
    To assess the immunogenicity of MEDI0457 and Durvalumab
  • Objective Response Rate (ORR) [ Time Frame: From time First dose of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab in as-treated patients
  • Progression Free Survival (PFS) [ Time Frame: From time First dose of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab
  • Disease control Rate (16Weeks) [ Time Frame: From time First dose of study medication through 5 years ]
    To assess anti-tumor activity in MEDI0457 plus Durvalumab
  • Overall Survival (OS) [ Time Frame: From time First dose of of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab
  • Durva serum cTrough concentration for Pharmacokinetics [ Time Frame: From time of informed consent through 28 days post end of treatment ]
    To assess the pharmacokinetics of Durvalumab
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of MEDI0457 and Durvalumab in Patients With HPV Associated Recurrent/Metastatic Head and Neck Cancer
Official Title  ICMJE A Phase 1b/2a, Multi-Center Open-Label Study to Evaluate the Safety and Efficacy of Combination Treatment With MEDI0457 (INO-3112) and Durvalumab (MEDI4736) in Patients With Recurrent/Metastatic HPV Associated Head and Neck Squamous Cancer
Brief Summary

This is a Phase 1b/2a, open-label, multi-center study to evaluate the safety and tolerability, anti-tumor activity, and immunogenicity of MEDI0457 (also known as INO 3112) a HPV DNA vaccine in combination with durvalumab (also known as MEDI4736) which is a human monoclonal antibody directed against PD-L1, which blocks the interaction of PD-L1 with PD-1 and CD80.

An initial three to 12 patients (Safety Analysis Run-in patients) will be enrolled and assessed for safety before additional patients are enrolled.

The initial safety analysis run-in patients along with an approximate total of 50 patients with human papilloma virus associated recurrent or metastatic head and neck squamous cell cancer will be enrolled in this study and evaluated also for anti-tumor efficacy to MEDI0457 in combination with durvalumab.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Head and Neck Cancer
  • Human Papilloma Virus
Intervention  ICMJE
  • Drug: MEDI0457
    MEDI0457 Administration by IM injection followed by electroporation (EP) using CELLECTRA®5P device.
  • Device: CELLECTRA®5P device (CELLECTRA 2000)
    MEDI0457 Administration by IM injection followed by electroporation (EP) using CELLECTRA®5P device.
  • Drug: Durvalumab
    Durvalumab will be administered intravenously at a dose of 1500mg every 4 weeks.
Study Arms  ICMJE Experimental: HPV associated recurrent/metastatic HNSCC
Approximately 50 patients with HPV associated recurrent/metastatic HNSCC
Interventions:
  • Drug: MEDI0457
  • Device: CELLECTRA®5P device (CELLECTRA 2000)
  • Drug: Durvalumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 4, 2019)
35
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2017)
40
Estimated Study Completion Date  ICMJE March 19, 2021
Estimated Primary Completion Date March 19, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male and female subjects 18 years and older
  2. Histologically or cytologically confirmed diagnosis of HNSCC associated with HPV by a p16 immunohistochemistry (IHC) assay or HPV-16 or HPV-18 positive by nucleic acid testing.
  3. Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
  4. Patients who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.

Exclusion criteria:

  1. Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease with some exceptions.
  2. Current or prior use of immunosuppressive medication within 14 days prior to first study dose, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed.
  3. No prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g., anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03162224
Other Study ID Numbers  ICMJE D8860C00005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MedImmune LLC Study Director
PRS Account MedImmune LLC
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP