Pembrolizumab in HNSCC With Residual Disease After Radiation
Condition: Head and Neck Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Pembrolizumab
Intervention description: a constant dose of 200 mg every three weeks, for four cycles.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase II study for patients with squamous cell carcinoma of the head and neck who
      have residual disease following definitive therapy with radiation (with or without systemic
      therapy). Patients must be diagnosed with residual disease within 24 weeks of completion of
      radiation therapy. Residual disease must be biopsy proven before the patient can consent to
      the trial, and can be either from lymph nodes in the neck, or from the primary tumor site.
      Prior to beginning study therapy patients are evaluated by an ENT to determine if they have
      disease amenable to surgical resection. Both resectable and unresectable patients will be
      eligible for participation in the study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent/assent for the trial.

          2. Be => 18 years of age on day of signing informed consent.

          3. Biopsy proven residual disease.

          4. Be willing to provide tissue from a newly obtained core biopsy of a tumor lesion.
             Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to
             initiation of treatment on Day 1 and following completion of RT/CRT.

          5. Have a performance status of 0 or 1 or 2 on the ECOG Performance Scale.

          6. Demonstrate adequate organ function. Labs value need to be assessed within 14 days of
             study treatment.

          7. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          8. Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication (Reference
             Section 5.7.2). Subjects of childbearing potential are those who have not been
             surgically sterilized or have not been free from menses for > 1 year.

          9. Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.

         10. Patients must have a history of Stage I-IVB SCC of the head and neck arising from the
             oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx and must have been
             treated with definitive intent radiation (with or without systemic therapy)

         11. Patients must be at least 6 weeks (42 days) and no more than 24 weeks (168 days) from
             completion of radiation with or without systemic therapy at the time of biopsy
             confirming residual disease. Patients must receive the first dose of study medication
             no more than 28 weeks following completion of radiation.

         12. Patients must have pathological evidence of persistent lymph node disease or
             persistent disease at the primary tumor site with viable tumor cells confirmed by a
             biopsy within 24 weeks of study treatment and no evidence of metastatic disease
             following primary radiation with or without systemic therapy confirmed by a CT scan
             within 4 weeks of study treatment. If a biopsy confirming residual disease has not
             been performed, this can be performed after obtaining consent during the screening
             procedures.

         13. Persistent lymph node disease with viable tumor cells will be determined by the
             histological determination of tumor viability.

         14. All persistent disease must have received at least 66 Gy in 1.8-2Gy fractions of
             radiotherapy to the area of residual disease (or a biologically equivalent dose given
             by the linear quadratic equation: biologically equivalent dose (BED) = nd (1 + d/(
             α/β), where n is the number of fractions, d dose per fraction and the α/β ratio for
             tumor is 10. Previous radiation records will be obtained to confirm adequate dosing.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          2. Has a diagnosis of immunodeficiency or is receiving supraphysiologic doses of systemic
             steroid therapy or any other form of immunosuppressive therapy within 7 days prior to
             the first dose of trial treatment. A physiologic dose of steroids is defined as up to
             10mg of prednisone daily (or its equivalent).

          3. Has a known history of active TB (Bacillus Tuberculosis)

          4. Hypersensitivity to pembrolizumab or any of its excipients.

          5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from acute,
             non-hematological adverse events due to agents administered more than 4 weeks earlier,
             unless otherwise approved by the Principal Investigator.

               -  Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤
                  Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any
                  grade xerostomia, and any grade dysgeusia, are an exception to this criterion and
                  may qualify for the study. Also please note that the presence of a feeding tube
                  to aid with nutrition does not disqualify patients from study.

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting
                  therapy.

          6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to the first protocol treatment or who has not recovered (i.e., ≤
             Grade 1 or at baseline) from acute, non-hematological adverse events due to a
             previously administered agent, unless otherwise approved by the Principal
             Investigator.

               -  Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤
                  Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any
                  grade xerostomia, and any grade dysgeusia, are an exception to this criterion and
                  may qualify for the study. Also please note that the presence of a feeding tube
                  to aid with nutrition does not disqualify patients from study.

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting
                  therapy.

          7. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          8. Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          9. Has 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 (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         10. Has known history of non-infectious pneumonitis that required steroids, or current
             pneumonitis.

         11. Has an active infection requiring systemic therapy.

         12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         13. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

         15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

         16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         18. Has received a live vaccine within 30 days of the first protocol treatment. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

         19. Any patient receiving adjuvant systemic therapy following the completion of radiation
             therapy is ineligible.

         20. Any patient with evidence of distant metastatic disease on a CT within 4 weeks of
             treatment is ineligible.

         21. Evidence of interstitial lung disease.