Clinical Trials /

Neoadjuvant-Adjuvant Pembrolizumab in Resectable Advanced Basal Cell Carcinoma of H&N

NCT04323202

Description:

The purpose of this study is to evaluate anti-PD-1 Neoadjuvant therapy in Basal cell carcinoma to provide a better outcome when administered prior to surgery and provide a therapeutic strategy to avoid surgery altogether. The study team will gather information about how Basal cell carcinoma responds to Pembrolizumab prior to surgery and to gather information about recurrence rates. Pembrolizumab, is an investigational (experimental) drug that may improve the response of the immune system against cancer. Pembrolizumab is a manufactured antibody, much like the antibodies usually made by the human body to fight off infection. The idea behind developing this experimental drug is to stimulate the body's immune system to kill cancer cells. Pembrolizumab antibody has been specifically made to block a program cell death-1 (PD-1) protein receptor, which is found on cells of the immune system. PD-1 receptor seems to slow down the immune response. Blocking PD-1 with pembrolizumab antibody may make the immune response more active and may improve the response of the immune system against cancer. Pembrolizumab is currently FDA approved for use in other malignancies. It has been used to treat a number of other diseases such as certain types of lung cancer, cervical cancer and lymphoma. The use of Pembrolizumab in this study is experimental because it is not approved by the Food and Drug Administration (FDA) for use in the treatment of Basal cell carcinoma.

Related Conditions:
  • Basal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant-Adjuvant Pembrolizumab in Resectable Advanced Basal Cell Carcinoma of H&N
  • Official Title: A Phase 1B, Single Arm Study of Neoadjuvant-Adjuvant Pembrolizumab in Resectable Advanced Basal Cell Carcinoma of the Head and Neck to Assess for Pathologic Responses in the Tumor Microenvironment

Clinical Trial IDs

  • ORG STUDY ID: CASE10319
  • NCT ID: NCT04323202

Conditions

  • Basal Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
PembrolizumabPermbrolizumab

Purpose

The purpose of this study is to evaluate anti-PD-1 Neoadjuvant therapy in Basal cell carcinoma to provide a better outcome when administered prior to surgery and provide a therapeutic strategy to avoid surgery altogether. The study team will gather information about how Basal cell carcinoma responds to Pembrolizumab prior to surgery and to gather information about recurrence rates. Pembrolizumab, is an investigational (experimental) drug that may improve the response of the immune system against cancer. Pembrolizumab is a manufactured antibody, much like the antibodies usually made by the human body to fight off infection. The idea behind developing this experimental drug is to stimulate the body's immune system to kill cancer cells. Pembrolizumab antibody has been specifically made to block a program cell death-1 (PD-1) protein receptor, which is found on cells of the immune system. PD-1 receptor seems to slow down the immune response. Blocking PD-1 with pembrolizumab antibody may make the immune response more active and may improve the response of the immune system against cancer. Pembrolizumab is currently FDA approved for use in other malignancies. It has been used to treat a number of other diseases such as certain types of lung cancer, cervical cancer and lymphoma. The use of Pembrolizumab in this study is experimental because it is not approved by the Food and Drug Administration (FDA) for use in the treatment of Basal cell carcinoma.

Detailed Description

      This is a phase 1 study looking at anti-PD-1 Neoadjuvant therapy in Basal cell carcinoma in
      participants with locoregionally advanced, but resectable basal cell carcinoma of the head
      and neck. Participants will undergo fine cut CT imaging (head and neck) and treatment with
      the study drug pembrolizumab.

      The primary objective of this study is to evaluate pathologic response to pre-operative
      treatment of pembrolizumab in the study group.

      Secondary objectives of this study include assessing safety of the intervention, and
      assessing phenotyping immune infiltrates in non-pathology complete responders (pCRs), as well
      as assessment of changes to the systemic immune system (e.g. peripheral blood lymphocytes
      (PBLs)) in pCRs vs partial responders (pPR) vs non responders.

      The exploratory objective will include assessing one-year recurrence rates after completion
      of NeoAdjuvant-Adjuvant therapy.
    

Trial Arms

NameTypeDescriptionInterventions
PermbrolizumabExperimentalParticipants will undergo fine cut CT imaging (head and neck) followed by at least 4 doses of pembrolizumab q 3 weeks. After the 4th dose of pembrolizumab as appropriate, patients will undergo standard surgical resection, with all non-marginal tissue as well as the pre-op biopsy to be stored for collateral research. 2 weeks after initial flap or graft insert (which would be equivalent to stage 1 of a forehead flap) patients would continue for a total of approximately 1 year of pembrolizumab q 3 weeks (another 13 doses, thus 17 doses total).
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Advanced basal cell carcinoma for the purposes of this study will be defined by
             features associated with increased risk of recurrence including at least one of the
             following:

               -  >=20mm

               -  Meeting indication for post-operative radiation

               -  Perineural invasion in multiple nerves

          -  Female participants: A female participant is eligible to participate if she is not
             pregnant (see Appendix 3), not breastfeeding, and at least one of the following
             conditions applies:

               -  Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR

               -  A female of child bearing potential who agrees to follow the contraceptive
                  guidance in Appendix 3 during the treatment period and for at least 150 days
                  after the last dose of study treatment.

          -  The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial.

          -  Have a histological confirmation of diagnosis of Basal cell carcinoma (BCC) of any
             subtype (e.g. Nodular, aggressive infiltrative, etc).

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed within 7 days prior to the date of
             allocation/randomization. Patients with PS 2 will be considered if good rationale
             provided and discussed with Merck study team.

          -  Have adequate organ function as defined in the following table (Table 1). Specimens
             must be collected within 10 days prior to the start of study treatment.

          -  Must not be on active immunosuppression, have a history of life threating virus, have
             had other (beside non-melanoma skin cancers, or recent indolent cancers e.g.: resected
             low grade prostate cancer) cancer diagnoses in the last two years, or have had
             immunotherapy of any kind within the last 2 years.

        Must not have a history of (non-infectious) pneumonitis that required steroids or has
        current pneumonitis.

          -  Participants who require adjuvant radiation are eligible.

        Adequate Organ Function Laboratory Values Note: This table includes eligibility-defining
        laboratory value requirements for treatment; laboratory value requirements should be
        adapted according to local regulations and guidelines for the administration of specific
        chemotherapies.

        System (Hematological)

          -  Absolute neutrophil count (ANC)

               -  >= 1500/μL

          -  Platelets >= 100 000/μL

          -  Hemoglobin

               -  >= 9.0 g/dL or >= 5.6 mmol/L ---- Criteria must be met without erythropoietin
                  dependency and without packed red blood cell (pRBC) transfusion within last 2
                  weeks

        System (Renal)

          -  Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in
             place of creatinine or CrCl) --- <=1.5 × ULN OR >= 30 mL/min for participant with
             creatinine levels > 1.5 × institutional ULN ---- Creatinine clearance (CrCl) should be
             calculated per institutional standard.

        System (Hepatic)

          -  Total bilirubin

             --- <=1.5 ×ULN OR direct bilirubin <= ULN for participants with total bilirubin levels
             >1.5 × ULN

          -  Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) [AST (SGOT)] and
             alanine aminotransferase (serum glutamic pyruvic transaminase) [ALT (SGPT)] --- <= 2.5
             × ULN (≤5 × ULN for participants with liver metastases)

        System (Coagulation)

          -  International normalized ratio (INR) OR prothrombin time (PT)

          -  Activated partial thromboplastin time (aPTT) --- <= 1.5 × ULN unless participant is
             receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of
             intended use of anticoagulants

        Exclusion Criteria:

          -  A female of child bearing potential who has a positive urine pregnancy test within 72
             hours prior to enrollment (see Appendix 3). If the urine test is positive or cannot be
             confirmed as negative, a serum pregnancy test will be required. In the event that 72
             hours have elapsed between the screening pregnancy test and the first dose of study
             treatment, another pregnancy test (urine or serum) must be performed and must be
             negative in order for subject to start receiving study medication.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
             OX-40, CD137).

          -  Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks prior to enrollment. Participants must have recovered from all AEs due
             to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy
             may be eligible. If participant received major surgery, they must have recovered
             adequately from the toxicity and/or complications from the intervention prior to
             starting study treatment.

          -  Has received prior radiotherapy within 2 weeks of start of study treatment.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

          -  Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment.

        Note: Participants who have entered the follow-up phase of an investigational study may
        participate as long as it has been 4 weeks after the last dose of the previous
        investigational agent.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 2 years. Note: Participants with other types of skin carcinoma or
             carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone
             potentially curative therapy are not excluded.

          -  Has known active CNS metastases and/or carcinomatous meningitis. Participants with
             previously treated brain metastases may participate provided they are radiologically
             stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
             (note that the repeat imaging should be performed during study screening), clinically
             stable and without requirement of steroid treatment for at least 14 days prior to
             first dose of study treatment.

          -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

          -  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.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a known history of Human Immunodeficiency Virus (HIV).

          -  Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
             reactive) or known active Hepatitis C virus (defined as: HCV RNA >800,000 IU/L is
             detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
             unless mandated by local health authority.

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

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, 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 study, starting with the screening visit through 120 days
             after the last dose of trial treatment.

          -  History of Hedgehog inhibitor treatment for any reason.

          -  History of allogeneic tissue/solid organ transplant whether or not on active
             immunosuppression.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic response as assessed by change in tumor volume (RECIST 1.1)
Time Frame:At time of surgery (85 days)
Safety Issue:
Description:Pathologic response as assessed by change in tumor volume. Lesions measured between baseline and surgery using RECIST 1.1 criteria

Secondary Outcome Measures

Measure:Number of participants experiencing a grade 3 or higher Adverse Event
Time Frame:up to 30 days after treatment
Safety Issue:
Description:Safety assessed by number of participants experiencing a grade 3 or higher Adverse Event
Measure:Number of changes to surgical field which could negatively influence resection
Time Frame:At time of surgery (85 days)
Safety Issue:
Description:Number of changes to surgical field which could negatively influence resection such as excessive inflammation or infection.
Measure:Rates of phenotyping immune infiltrates in non pCR
Time Frame:At baseline, at day 64, and post-op up to 2 years
Safety Issue:
Description:Rates of phenotyping immune infiltrates in non pCR characterized as 'rare', 'moderate', or 'brisk'. Blood for this outcome will be collected at baseline, at day 64 and at recurrence up to 2 years.
Measure:One-year recurrence rates after completion of neoadjuvant-adjuvant therapy
Time Frame:1 year
Safety Issue:
Description:One-year recurrence ratesafter completion of neoadjuvant-adjuvant therapy
Measure:One-year recurrence rates after neoadjuvant therapy
Time Frame:1 year
Safety Issue:
Description:One-year recurrence rates after pembrolizumab neoadjuvant therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Brian Gastman

Last Updated

March 24, 2020