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Reirradiation With Pembrolizumab in Locoregional Inoperable Recurrence or Second Primary Squamous Cell CA of the Head and Neck

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ClinicalTrials.gov Identifier: NCT02289209
Recruitment Status : Recruiting
First Posted : November 13, 2014
Last Update Posted : February 9, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Dan Zandberg, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE October 17, 2014
First Posted Date  ICMJE November 13, 2014
Last Update Posted Date February 9, 2021
Actual Study Start Date  ICMJE January 10, 2019
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
Progression free survival [ Time Frame: Up to 36 months (after starting reirradiation and MK-3475) ]
Number of months from the date of initiation of treatment to the date of progression of disease or death (whichever occurs first). Progressive disease, per RECIST 1.1, is defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Original Primary Outcome Measures  ICMJE
 (submitted: November 12, 2014)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • Overall Response Rate (ORR) [ Time Frame: Up to 36 months (after initiation of treatment with reirradiation and MK-3475) ]
    Overall response rate, which will be determined per RECIST 1.1, is defined as the percentage of the patients who have a either Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, or, Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The patient's best overall response rate defined as the best response recorded from the start of the treatment until disease progression will be recorded.
  • Time to in field disease progression [ Time Frame: Up to 36 months (after initiation of treatment with reirradiation and MK-3475) ]
    Number of months from initiation of treatment to progression of disease within the radiation field.Progressive disease, per RECIST 1.1, is defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
  • Overall survival (OS) [ Time Frame: Up to 36 months (after initiation of treatment with reirradiation and MK-3475) ]
    Number of months from first treatment until death. Patients who are alive will be censored at the last date of patient contact.
  • Quality of life using EORTC QLQ-C30 and EORTC QLQ-H&N 35 [ Time Frame: Up to 36 months (after initiation of treatment with reirradiation and MK-3475) ]
    Patient reported outcomes will be measured using EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires. This tool contains 30 items. It measures 5 functional dimensions (physical, role, cognitive, social, emotional), 6 single items (appetite loss, constipation, dyspnea, financial impact, sleep disturbance, diarrhea), 3 symptom items (fatigue, pain, nausea/vomiting) and a global health and quality of life scale. Scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 36 months (after initiation of treatment with reirradiation and MK-3475) ]
    The percentage of patients that have achieved a complete response, partial response, and stable disease as defined by RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, or Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2014)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reirradiation With Pembrolizumab in Locoregional Inoperable Recurrence or Second Primary Squamous Cell CA of the Head and Neck
Official Title  ICMJE A Phase II Trial of Reirradiation Combined With Open Label Pembrolizumab in Patients With Locoregional Inoperable Recurrence or Second Primary Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Brief Summary 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®).
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Head and Neck Cancer
  • Carcinoma, Squamous Cell of Head and Neck
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Radiation: Reirradiation
  • Drug: MK-3475
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 12, 2014)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Ruth, RN 412-623-8963 ruthj2@upmc.edu
Contact: Samantha Demko, RN 412-6479015 albesl@upmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02289209
Other Study ID Numbers  ICMJE HCC 18-009
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: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dan Zandberg, University of Pittsburgh
Study Sponsor  ICMJE Dan Zandberg
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Dan Zandberg, MD UPMC Hillman Cancer Center
PRS Account University of Pittsburgh
Verification Date February 2021

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