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Reirradiation With MK-3475 (Pembrolizumab) in Locoregional Inoperable Recurrence or Second Primary Squamous Cell CA of the Head and Neck

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by Dan Zandberg, University of Maryland
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Dan Zandberg, University of Maryland
ClinicalTrials.gov Identifier:
NCT02289209
First received: October 17, 2014
Last updated: March 30, 2017
Last verified: March 2017
  Purpose
Eligible participants with locoregional inoperable recurrence or second primary squamous cell carcinoma of the head and neck will be treated with reirradiation combined with anti-PD-1 mAb MK-3475 (generic name: pembrolizumab, trade name Keytruda®).

Condition Intervention Phase
Recurrent Head and Neck Cancer Carcinoma, Squamous Cell of Head and Neck Radiation: Reirradiation Drug: MK-3475 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Reirradiation Combined With Open Label MK-3475 in Patients With Locoregional Inoperable Recurrence or Second Primary Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Resource links provided by NLM:


Further study details as provided by Dan Zandberg, University of Maryland:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: Up to 36 months after starting reirradiation and MK-3475 ]
    Progression free survival will be measured in all patients with locoregional inoperable recurrence or second primary squamous cell carcinoma of the head and neck treated with reirradiation in combination with MK-3475.


Secondary Outcome Measures:
  • Incidence and severity of adverse events from reirradiation and/or MK-3475. [ Time Frame: Up to 36 months after starting reirradiation and MK-3475 ]
    Adverse events will be recorded for all patients after starting combination radiation and MK-3475 therapy.

  • Best overall response rate (ORR) [ Time Frame: Up to 36 months after starting treatment with reirradiation and MK-3475 ]
    Best overall response rate will be assessed using RECIST 1.1 in patients treated with reirradiation in combination with MK-3475

  • Time to in field disease progression will be assessed using RECIST 1.1 [ Time Frame: Up to 36 months after starting treatment with reirradiation and MK-3475 ]
    Time to in field disease progression will be assessed using RECIST 1.1

  • Overall survival (OS) [ Time Frame: Up to 36 months after starting combination reirradiation and MK-3475 ]
    The length of overall survival will be measured in patients treated with reirradiation in combination with MK-3475.

  • Subject quality of life as measured by the EORTC QLQ-C-30 and EORTC QLQ-H&N 35 [ Time Frame: Up to 36 months after starting combination reirradiation and MK-3475 ]
    Quality of life will be assessed using the EORTC QLQ-C30 and EORTC QLQ-H&N 35.

  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 36 months after starting combination reirradiation and MK-3475 ]
    Clinical Benefit Rate will be assessed using RECIST 1.1 in patients treated with reirradiation in combination with MK-3475


Estimated Enrollment: 48
Study Start Date: December 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reirradiation + MK-3475
Reirradiation 1.2 Gy BID for 5 days a week for 5 weeks with MK-3475 (Keytruda, pembrolizumab) 200mg intravenous every 3 weeks until 3 months post completion of reirradiation.
Radiation: Reirradiation
Reirradiation 1.2 GY BID 5 days a week for 5 weeks.
Drug: MK-3475
MK-3475 will be given at 200mg intravenous every 3 weeks starting day one of reirradiation and will be continued once every 3 weeks until 3 months post completion of reirradiation. Further continuation of MK-3475 will be determined by response evaluation at 3 months post completion of reirradiation
Other Name: Keytruda, pembrolizumab

Detailed Description:

Each participant will undergo screening and then be treated with reirradiation with 1.2 Gy BID, 5 days a week (weeks 1-5). MK-3475 (generic name: pembrolizumab, trade name Keytruda®) will be given at 200mg intravenous every 3 weeks starting day one of reirradiation and will be continued in all participants until 3 months post completion of reirradiation, at which time a PET/CT will be done to evaluate response. Participants with progressive disease (PD) will be taken off MK-3475 and followed for survival. Participants that have a complete response (CR) will be followed clinically and radiographically, and if disease recurs may be eligible to be retreated with MK-3475 for up to one year. Participants with partial response (PR) or stable disease (SD) will continue treatment with MK-3475 for up to two years unless one of the following occurs:

  • documented disease progression
  • unacceptable adverse event(s)
  • intercurrent illness that prevents further administration of treatment
  • investigator decision to withdraw the subject
  • withdrawal of consent
  • pregnancy
  • noncompliance
  • administrative reasons (i.e. trial is closed prematurely).

Participants who have not progressed at completion of 24 months of therapy will be observed, but may be eligible for 1 year of retreatment with MK-3475 if they develop recurrence/progression and qualify for retreatment as detailed in the protocol,and if the trial is still ongoing.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Patients with biopsy proven locoregional recurrence or second primary SCCHN which is unresectable or the patient is unwilling to undergo resection. Determination of unresectability will be based on multidisciplinary review of each case.

Inclusion Criteria:

  1. Have received only prior radiation treatment course. Prior radiation course must have been with curative intent.
  2. At least 6 months since completion of radiation
  3. Based on prior radiation records, have had most of the tumor volume (>50%) previously radiated at doses > 45 Gy without exceeding spinal cord tolerance (combining previous and future radiation dose to spinal cord of < 50 Gy).
  4. Be willing to undergo percutaneous endoscopic gastrostomy (PEG) placement, if necessary.
  5. Have at least one measurable area of disease based on RECIST 1.1 within the previously radiated field.
  6. Have provided adequate tissue for PD-L1 analysis either from an archival tissue sample or fresh biopsy done to confirm recurrence/second primary. Archival tissue sample can only be used if done within 3 months of enrollment on the clinical trial.
  7. Performance status of 0 or 1 on the ECOG Performance Scale.
  8. Life expectancy greater than 12 weeks
  9. Adequate organ function as defined by the protocol

Exclusion Criteria:

  1. Presence of distant metastatic disease.
  2. Is currently participating in or has participated in a study of an investigational agent or used an investigational device within 4 weeks of the first dose of treatment.
  3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  4. Has had a prior monoclonal antibody, chemotherapy, or targeted small molecule therapy within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
  5. History of other malignancy within 5 years with the exception of prior Squamous cell carcinoma of the head and neck, adequately treated basal cell or squamous cell skin cancer, or carcinoma of the cervix.
  6. Has an active autoimmune disease
  7. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  8. Has an active infection requiring systemic therapy
  9. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  10. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  11. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  12. Has received a live vaccine within 30 days prior to the first dose of trial treatment
  13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
  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: NCT02289209

Contacts
Contact: Navid Saeidi 410-328-6465 Navid.saeidi@umm.edu
Contact: Dan Zandberg, MD 410-328-6373 dzandberg@umm.edu

Locations
United States, Maryland
University of Maryland Greenebaum Cancer Center 22 S. Greene Street Recruiting
Baltimore, Maryland, United States, 21201
Contact: Navid Saeidi    410-328-6465    navid.saeidi@umm.edu   
Contact: Dan Zandberg, MD    410-328-6373    dzandberg@umm.edu   
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Ana Kiess, MD    410-502-8000    akiess1@jhmi.edu   
Contact: Megan Kummerlowe, BS    410-502-2971    mkummer1@jhmi.edu   
Principal Investigator: Ana Kiess, MD         
United States, New York
Perlmutter Cancer Center - NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Zujun Li, MD    212-731-6465    zujun.li@nyumc.org   
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadephia, Pennsylvania, United States, 19111
Contact: Thomas Galloway, MD    215-728-4300    thomas.galloway@fccc.edu   
Principal Investigator: Thomas Galloway, MD         
Sponsors and Collaborators
Dan Zandberg
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Dan Zandberg, MD University of Maryland Greenebaum Cancer Center
  More Information

Responsible Party: Dan Zandberg, Assistant Professor of Medicine, University of Maryland
ClinicalTrials.gov Identifier: NCT02289209     History of Changes
Other Study ID Numbers: 1456GCC, HP-00061458
Study First Received: October 17, 2014
Last Updated: March 30, 2017

Keywords provided by Dan Zandberg, University of Maryland:
head and neck cancer
reirradiation
MK-3475
Anti-PD-1 monoclonal antibody
Squamous cell carcinoma
Keytruda
pembrolizumab

Additional relevant MeSH terms:
Carcinoma
Head and Neck Neoplasms
Recurrence
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Disease Attributes
Pathologic Processes
Neoplasms, Squamous Cell
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 21, 2017