Clinical Trials /

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

NCT02289209

Description:

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®).

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Reirradiation With Pembrolizumab in Locoregional Inoperable Recurrence or Second Primary Squamous Cell CA of the Head and Neck
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: HCC 18-009
  • NCT ID: NCT02289209

Conditions

  • Recurrent Head and Neck Cancer
  • Carcinoma, Squamous Cell of Head and Neck

Interventions

DrugSynonymsArms
MK-3475Keytruda, pembrolizumabReirradiation + MK-3475

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®).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Reirradiation + MK-3475ExperimentalReirradiation 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.
  • MK-3475

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:Up to 36 months (after starting reirradiation and MK-3475)
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 36 months (after initiation of treatment with reirradiation and MK-3475)
Safety Issue:
Description:Overall response rate will 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.
Measure:Time to in field disease progression
Time Frame:Up to 36 months (after initiation of treatment with reirradiation and MK-3475)
Safety Issue:
Description: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).
Measure:Overall survival (OS)
Time Frame:Up to 36 months (after initiation of treatment with reirradiation and MK-3475)
Safety Issue:
Description:Number of months from first treatment until death. Patients who are alive will be censored at the last date of patient contact.
Measure: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)
Safety Issue:
Description: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.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 36 months (after initiation of treatment with reirradiation and MK-3475)
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dan Zandberg

Trial Keywords

  • head and neck cancer
  • reirradiation
  • MK-3475
  • Anti-PD-1 monoclonal antibody
  • Squamous cell carcinoma
  • Keytruda
  • pembrolizumab

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