Clinical Trials /

SBRT +/- Pembrolizumab in Patients With Local-Regionally Recurrent or Second Primary Head and Neck Carcinoma

NCT03546582

Description:

This phase II trial with a safety run-in component will evaluate whether the addition of pembrolizumab to Stereotactic Body Radiation Therapy (SBRT) re-irradiation will improve the progression-free survival for patients with recurrent or new second primary Head and Neck Squamous Cell Carcinoma (HNSCC).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SBRT +/- Pembrolizumab in Patients With Local-Regionally Recurrent or Second Primary Head and Neck Carcinoma
  • Official Title: KEYSTROKE: A Randomized Phase II Study of Pembrolizumab (KEYTRUDA®) Plus Stereotactic Re-irradiation Versus SBRT Alone for Locoregionally Recurrent or Second Primary Head and Neck Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: RTOG 3507
  • NCT ID: NCT03546582

Conditions

  • Head and Neck Squamous Cell Carcinoma (HNSCC)

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaArm I

Purpose

This phase II trial with a safety run-in component will evaluate whether the addition of pembrolizumab to Stereotactic Body Radiation Therapy (SBRT) re-irradiation will improve the progression-free survival for patients with recurrent or new second primary Head and Neck Squamous Cell Carcinoma (HNSCC).

Detailed Description

      Safety Run-In:

      To evaluate the safety of the addition of pembrolizumab (anti PD-1 immunotherapy) to
      re-irradiation with SBRT for patients with recurrent or new second primary head and neck
      squamous cell carcinoma (HNSCC).

      Phase II:

      To compare progression-free survival (PFS) for patients with recurrent or new second primary
      head and neck squamous cell carcinoma with SBRT re-irradiation with or without pembrolizumab.

      OUTLINE:

      Safety Run-In: Patients receive SBRT over 2 weeks and then receive pembrolizumab every 3
      weeks for up to 2 years.

      Phase II: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive SBRT over 2 weeks and then receive pembrolizumab every 3 weeks for up
      to 2 years.

      ARM II: Patients receive SBRT over 2 weeks. Arm II patients who experience progressive
      disease within 2 years after the start of SBRT will be allowed to cross over to receive
      pembrolizumab for up to 2 years.

      After the completion of study treatment, patients are followed up every 6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm IExperimentalPatients receive Stereotactic Body Radiation Therapy (SBRT) over 2 weeks and then receive pembrolizumab every 3 weeks for up to 2 years.
  • Pembrolizumab
Arm IIOtherPatients receive Stereotactic Body Radiation Therapy (SBRT) over 2 weeks. Arm II patients who experience progressive disease within 2 years after the start of SBRT will be allowed to cross over to receive pembrolizumab for up to 2 years.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically or cytologically-confirmed diagnosis of locoregional recurrent or any
                 new primary squamous cell carcinoma of the head and neck that is not amenable to
                 curative resection. A new primary HNSCC is defined where any one of the following
                 criteria are met:
    
                   -  Metachronous invasive SCC developing ≥ 6 months after an index HNSCC, more than 3
                      cm from the index lesion;
    
                   -  SCC developing in the same region as the index SCC if ≥ 36 months after the index
                      diagnosis and if within 3 cm of a site where disease was completely resected or
                      complete response was documented;
    
                   -  New SCC that is cytologically or molecularly distinct from index SCC (eg new HPV
                      negative SCC with prior index SCC that was HPV positive).
    
              -  Tumor tissue testing for p16 status is required for base of tongue, soft palate, and
                 tonsil cancer. If a p16 testing has been previously performed on an oropharynx cancer
                 that has recurred, then repeat testing for p16 status is not required. Participants
                 whose first cancer was an unknown primary must have p16 testing from either the new
                 primary tumor or the recurrent cancer.
    
              -  Prior radiotherapy (RT) to the head and neck (30 Gy minimum)
    
              -  Disease must be limited to a single site or adjacent sites that can be treated in a
                 single contiguous target volume for which the maximum total tumor dimension (GTV) must
                 be <7.5cm. Examples of eligible patients include:
    
                   1. A primary site recurrence in the oropharynx with a concurrent level 2 nodal mass,
                      or a laryngeal recurrence with a level 3 nodal mass
    
                   2. Multiple nodes in the same (level 2) or adjacent nodal levels (levels 2 and 3)
    
                   3. Skull base recurrence with a lateral pharyngeal or high level 2 node
    
            Note: These cases will be eligible provided that the maximum total tumor dimension is
            <7.5cm. For cases in which a tumor biopsy was performed and there is a biopsy/tumor
            debulking bed adjacent to the gross residual disease, all of the preoperative radiographic
            abnormalities must be included in the GTV and meet the <7.5cm maximal dimension criteria to
            meet eligibility.
    
            Note: Patients who meet these criteria only after surgical removal of a portion of the
            patient's disease (e.g. removal of level 4 nodal mass in a patient with a tongue base
            primary; or of a contralateral nodal mass in an N2c patient) are ineligible.
    
              -  Patients who have undergone a recent biopsy (e.g. incisional) are eligible. Any
                 preceding surgical procedure beyond a biopsy (e.g. debulking) must be reviewed as
                 follows:
    
                   -  Patients rendered free of gross disease are not eligible.
    
                   -  Patients with gross residual disease postoperatively, must be reviewed by the
                      Surgical Co-PI for determination of eligibility.
    
                   -  Patients eligible for study must have cutaneous wounds healed for 4-6 weeks prior
                      to the initiation of SBRT.
    
              -  History/physical examination within 56 days prior to entry
    
              -  Examination by a Radiation Oncologist and Medical Oncologist within 56 days prior to
                 entry; [Note: Baseline dental assessment is strongly recommended prior to start of
                 therapy but is not required for eligibility]
    
              -  Contrast enhanced CT or MRI, of the tumor and neck within 56 days prior to entry.
    
              -  Chest CT scan or full body PET/CT within 56 days prior to entry; patients with
                 equivocal pulmonary nodules that are < 1.5 cm, that cannot be safely biopsied, or that
                 are negative on PET/CT imaging are eligible.
    
              -  Zubrod Performance Status of 0-1 within 28 days prior to entry.
    
              -  Age ≥ 18
    
              -  Trial is open to all genders
    
              -  Hematologic: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3, Platelets ≥ 100,000
                 cells/mm3, Hemoglobin ≥ 9 g/dL
    
              -  Hepatic: Total bilirubin ≤ 1.5 x ULN OR Direct bilirubin ≤ ULN for subjects with total
                 bilirubin levels > 1.5 x ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
    
              -  Creatinine ≤ 1.5 x ULN, OR measured or calculated creatinine clearance > 60 mL/min for
                 subject with creatinine levels > 1.5 x institutional ULN [NOTE: Calculated creatinine
                 per institutional standard; GFR may be used in place of creatinine or CrCl]
    
              -  Negative serum pregnancy test within 14 days prior to entry for women of childbearing
                 potential. (Note: A pregnancy test must be repeated within 3 days prior to the
                 administration of the first dose of pembrolizumab)
    
              -  The patient or legally authorized representative must provide study-specific informed
                 consent prior to study entry.
    
            Exclusion Criteria:
    
              -  Distant metastases.
    
              -  Tumors that involve more than 180 degrees of the carotid artery on diagnostic CT or
                 MRI of the neck within 56 days prior to entry. Investigators are encouraged to review
                 the CT simulation imaging and ensure that tumor progression has not occurred whereby
                 patients who were initially eligible based on diagnostic imaging, would be rendered
                 ineligible based on CT simulation imaging (e.g. tumor size >7.5cm, skin involvement,
                 >180 degrees of carotid encasement by tumor). If this does occur, the patient should
                 be removed from the study and the Radiation Oncology Co-PIs should be notified via
                 email. Note: It is strongly recommended that CT simulation be performed prior to
                 entry.
    
              -  Patients with gross skin involvement (i.e. tumor ulceration through the skin) are
                 excluded. Patients with tumor approaching the skin but in which the overlying skin
                 remains intact are eligible, providing that planning constraints can be achieved
                 without the use of bolus.
    
              -  Disease that requires two or more discontiguous target volumes will be ineligible.
                 Examples of such cases include:
    
                   -  Bilateral nodal targets
    
                   -  Level 2 and level 4 nodes
    
                   -  An oropharyngeal recurrence with a low level 4 node;
    
              -  Patients for whom the maximal total tumor dimension (GTV) is >7.5cm
    
              -  Prior radiation to primary tumor within 6 months of entry
    
              -  Prior systemic therapy, investigational agent or investigational device within 28 days
                 of start of study treatment.
    
              -  Surgical resection of the qualifying cancer is not permitted. (Patients who have
                 undergone biopsies are eligible). Patients without radiographically apparent gross
                 tumor are ineligible. For cases where an operation more extensive than a biopsy was
                 performed but radiographically apparent gross residual tumor remains, will be reviewed
                 by the Surgical Co-PI for determination of eligibility.
    
              -  No concurrent treatment with other investigational agent or investigational device.
    
              -  Prior therapy with a checkpoint inhibitor (eg anti-CTLA-4, anti-PD-1 or anti-PD-L1
                 therapy).
    
              -  Patients with immunodeficiency, or receiving systemic steroid, or any form of
                 immunosuppressive therapy at the time of registration (e.g. history of human
                 immunodeficiency virus - HIV). Use of physiologic doses corticosteroids may be
                 approved with consultation with study chairs.
    
              -  Active autoimmune disease that has required systemic treatment in the past 2 years
                 (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
                 drugs). Replacement therapy (e.g. thyroxin, insulin, or physiologic corticosteroid
                 replacement therapy for adrenal or pituitary insufficiency etc.) is not considered a
                 form of systemic therapy
    
              -  Known active hepatitis B (positive test for virus surface antigen - HBsAg) or
                 hepatitis C virus (e.g. positive HCV RNA qualitative test).
    
              -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
    
              -  Treatment with a live vaccine within 30 days of entry.
    
              -  Unstable angina and or congestive heart failure requiring hospitalization in the last
                 6 months.
    
              -  Myocardial infarction within the last 6 months.
    
              -  Active bacterial or fungal infection requiring intravenous antibiotic at the time of
                 entry
    
              -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                 requiring hospitalization or precluding study therapy within 30 days of entry.
    
              -  Other significant medical, surgical or psychiatric conditions or requirements for any
                 medication or treatment that in the opinion of the investigator may interfere with
                 compliance, make administration of anti-PD-L1 therapy hazardous, or obscure
                 interpretation of adverse events (AEs), such as a condition associated with frequent
                 diarrhea.
    
              -  Pregnancy, nursing females, or women of childbearing potential and men who are
                 sexually active and not willing/able to use medically acceptable forms of
                 contraception; this exclusion is necessary because the treatment involved in this
                 study may be significantly teratogenic.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression Free Survival (PFS)
    Time Frame:Assessed up to 5 years
    Safety Issue:
    Description:The time from randomization to the first documented progressive disease (PD) per RECIST 1.1 or death due to any cause, whichever comes first.

    Secondary Outcome Measures

    Measure:Overall Survival (OS)
    Time Frame:Assessed up to 5 years
    Safety Issue:
    Description:The time from randomization to death due to any cause.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:RTOG Foundation, Inc.

    Trial Keywords

    • HNSCC
    • Head and Neck Squamous Cell Carcinoma
    • KEYSTROKE

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