Clinical Trials /

The Addition of Pembrolizumab to Postoperative Radiotherapy in Cutaneous Squamous Cell Cancer of the Head and Neck

NCT03057613

Description:

A small group of skin cancers of the head and neck, called resected cutaneous squamous carcinomas, are more aggressive than most cancers of this type, even after being treated with standard therapy. This trial will use stronger treatment to look at the safety and effectiveness (efficacy) of combining a drug called Pembrolizumab with radiation after a cancer has already been treated to suppress secondary tumor formation in high risk cutaneous squamous cell cancer of the head and neck. Primary Objective To assess safety by looking at the people with dose limiting responses

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Addition of Pembrolizumab to Postoperative Radiotherapy in Cutaneous Squamous Cell Cancer of the Head and Neck
  • Official Title: A Phase II Study of the Addition of Pembrolizumab to Postoperative Radiotherapy in Resected High Risk Cutaneous Squamous Cell Cancer of the Head and Neck

Clinical Trial IDs

  • ORG STUDY ID: CASE6316
  • NCT ID: NCT03057613

Conditions

  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab + post operative radiotherapy

Purpose

A small group of skin cancers of the head and neck, called resected cutaneous squamous carcinomas, are more aggressive than most cancers of this type, even after being treated with standard therapy. This trial will use stronger treatment to look at the safety and effectiveness (efficacy) of combining a drug called Pembrolizumab with radiation after a cancer has already been treated to suppress secondary tumor formation in high risk cutaneous squamous cell cancer of the head and neck. Primary Objective To assess safety by looking at the people with dose limiting responses

Detailed Description

      Primary Objective:

      To assess safety and estimate 1-year PFS of postoperative radiation therapy (RT) +
      concurrent and adjuvant Pembrolizumab in high risk resected cutaneous squamous cell cancer
      of the head and neck (cSCC-HN).

      Secondary Objectives

        1. To evaluate the relationship of baseline programmed death-ligand 1 (PD-L1) expression
           by tumor and tumor-infiltrating lymphocytes (TILs) to preliminary efficacy .

        2. To phenotype tumor infiltrating lymphocytes and peripheral blood lymphocytes (PBLs),
           and investigate tumor suppressor populations including Tregs, myeloid-derived
           suppressor cells (MDSCs) and cluster of differentiation 8 (CD8) suppressor cells and
           assess ex vivo for effector function by cytokine production and cytotoxicity assays as
           well as suppressor function in assays with autologous PBLs.

        3. For those participants for whom tumor tissue is available, we will evaluate the tumor
           microenvironment (TME), and immune markers at the invasive margin of the tumor,
           including CD8, PD-1, PD-L1, T-cell immunoglobulin and mucin-domain containing-3
           (TIM-3), galectin-9 or high-mobility group protein 1 (HMGB-1), B- and T- lymphocyte
           attenuator (BTLA) and herpes virus entry mediator (HVEM), as well as
           lymphocyte-activation gene 3 (Lag-3), cytotoxic T-lymphocyte-associated protein 4
           (CTLA-4) and others.

        4. If sufficient tumor is available, we will also evaluate the genomic and/or
           transcriptomic profile of a subset of tumors using RNA-seq /Whole Transcriptome Shotgun
           Sequencing.

      Trial Design:

      This is a phase II trial evaluating the addition of concurrent and adjuvant fixed-dose
      pembrolizumab in combination with standard intensity-modulated radiation therapy (IMRT), in
      order to establish safety and estimate efficacy of this regimen to be tested in a subsequent
      randomized registration trial.

      Thirty seven patients will be enrolled.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + post operative radiotherapyExperimentalIMRT 60-66Gy for 6 weeks in combination with Pembrolizumab every 3 weeks for 16 weeks
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic diagnosis of cutaneous squamous cell carcinoma of the head and neck that
             has been resected with no evidence of gross residual disease (margin positivity is
             acceptable)

          -  Patients must have undergone resection of the disease and demonstrate high risk
             pathologic features including:

               -  T4

               -  Node positive disease

               -  T2/T3N0 disease with any 1 additional feature, including:

                    -  Recurrent Disease

                    -  Perineural invasion

                    -  Lymphovascular space invasion

                    -  Poorly differentiated histology

                    -  Positive Margins

                    -  Satellitosis or in-transit metastases

          -  Patients are required to have computerized tomography (CT) neck and chest or positron
             emission tomography/computerized tomography (PET/CT) and have no documented evidence
             of distant metastases

          -  Patients must not have a history of the following immunosuppressive conditions: bone
             marrow transplantation, lymphoid malignancies, or organ transplants and/or chronic
             rheumatic conditions that require active immunosuppressive therapy.

          -  Patients may not have had prior therapy with a checkpoint inhibitor (e.g.
             anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapy)

          -  Patients may not have had prior radiotherapy (>30Gy) to the area requiring treatment
             that would result in any overlap of tissue in both fields

          -  Patients may have received chemotherapy or radiation for a previous, curatively
             treated malignancy provided at least 2 years have elapsed and there is no current
             evidence of disease (patients with previous or concurrent additional skin cancers are
             eligible)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  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.

          -  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.
             Subjects of childbearing potential are those who have not been surgically sterilized
             or have not been free from menses for > 1 year.

          -  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.

          -  Patients must have adequate laboratory values

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelets ≥ 100,00/mcL

               -  Hemoglobin ≥ 9g/dL or ≥5.6mmol/L without transfusion

               -  Serum creatinine ≤ 1.5 times upper limit of normal (ULN) or measured creatinine
                  clearance ≥60mL/min for subject with creatinine levels >1.5 times institutional
                  ULN

               -  Serum bilirubin ≤ 1.5 times ULN or direct bilirubin ≤ ULN for subjects with
                  total bilirubin levels > 1.5 ULN

               -  Aspartate aminotransferase (AST (SGOT)) and alanine aminotransferase (ALT
                  (SPGT)) ≤ 2.5 times ULN or ≤ 5 times ULN for subjects with liver metastases

               -  Albumin ≥ 2.5mg/dL

               -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 times ULN
                  unless subject is receiving anticoagulant therapy as long as PT is within
                  therapeutic range of intended use of anticoagulants. Activated Partial
                  Thromboplastin Time (aPTT) ≤1.5 times ULN unless subject is receiving
                  anticoagulant therapy as long as PT or aPTT is within therapeutic range of
                  intended use of anticoagulants

        Exclusion Criteria:

          -  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.

          -  Has a known history of active Bacillus Tuberculosis (TB)

          -  Hypersensitivity to pembrolizumab.

          -  Has a history of the following immunosuppressive conditions: bone marrow
             transplantation, lymphoid malignancies, or organ transplants and/or chronic rheumatic
             conditions that require active immunosuppressive therapy

          -  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 adverse events due
             to agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiotherapy within 2
             weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline)
             from adverse events due to a previously administered agent.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or a separate primary squamous
             cell carcinoma of the skin.

          -  Has metastatic disease.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  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.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  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.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is
             detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with dose limiting toxicities
Time Frame:Up to 20 weeks post treatment
Safety Issue:
Description:There will be an initial safety run in cohort consisting of eight patients to allow for at least six evaluable patients for dose limiting toxicities (DLTs) by the week 20 visit. If a total of 0-2 of the initial six evaluable patients experience DLTs, the safety run in will have been deemed successful and the 29 remaining planned patients will be accrued. DLT for this study is defined as the occurrence of a severe adverse event (AE) that is at least possibly related to pembrolizumab, and occurs from the initiation of treatment thru 30 days after the final administration of the study treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • radiation
  • resected

Last Updated

March 27, 2017