Clinical Trials /

Pembrolizumab in Patients With Locally Advanced or Metastatic Skin Cancer

NCT02964559

Description:

This phase II trial studies how well pembrolizumab works in treating patients with skin cancer that has spread from where it started to nearby tissue, lymph nodes, or other parts of the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Patients With Locally Advanced or Metastatic Skin Cancer
  • Official Title: A Phase II Trial of Pembrolizumab (MK-3475) in Metastatic Cutaneous Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: IRB00087412
  • SECONDARY ID: NCI-2016-00831
  • SECONDARY ID: Winship3185-16
  • NCT ID: NCT02964559

Conditions

  • Recurrent Skin Carcinoma
  • Skin Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

This phase II trial studies how well pembrolizumab works in treating patients with skin cancer that has spread from where it started to nearby tissue, lymph nodes, or other parts of the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVE:

      -To establish the response rate of pembrolizumab in metastatic cutaneous squamous cell
      carcinoma.

      SECONDARY OBJECTIVES:

      -To determine the 6-month progression-free survival and 1 year overall survival of
      metastatic cutaneous squamous cell carcinoma of the skin (cSCC) treated with pembrolizumab.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat
      every 3 weeks in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 8-12
      weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  All subjects must have cutaneous squamous cell carcinoma that is not curable by
                 surgery or radiation; both locally advanced and metastatic squamous cell carcinoma
                 will be included.
    
              -  Be willing and able to provide written informed consent/assent for the trial.
    
              -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors
                 (RECIST) 1.1.
    
              -  Be willing to provide tissue from a newly obtained core or excisional 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. Subjects for whom newly-obtained
                 samples cannot be provided (e.g. inaccessible or subject safety concern) may submit
                 an archived specimen only upon agreement from the sponsor.
    
              -  Be willing to undergo normal skin biopsy prior to initiation of treatment and after
                 treatment.
    
              -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
                 performance scale.
    
              -  Absolute neutrophil count (ANC) ≥ 1,500/microliter (mcL)
    
              -  Platelets ≥ 100,000/mcL
    
              -  Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO)
                 dependency (within 7 days of assessment)
    
              -  Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated
                 creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
                 creatinine or creatinine clearance [CrCl]) ≥ 60 mL/min for subject with creatinine
                 levels > 1.5 X institutional ULN
    
              -  Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total
                 bilirubin levels > 1.5 ULN
    
              -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
                 alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X
                 ULN OR ≤ 5 X ULN for subjects with liver metastases
    
              -  Albumin ≥ 2.5 mg/dL
    
              -  International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless
                 subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
                 time (PTT) is within therapeutic range of intended use of anticoagulants.
    
              -  Activated partial thromboplastin rime (aPTT) ≤ 1.5 X ULN unless subject is receiving
                 anticoagulant therapy as long as PT or PTT is within therapeutic range of intended
                 use of anticoagulants.
    
              -  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.
    
            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 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, patients with human immunodeficiency virus (HIV) adequately
                 controlled on antiretrovirals (undetectable viral load) and patients with chronic
                 lymphocytic leukemia (CLL) not requiring systemic treatment will be included; in
                 addition, steroids for physiologic replacement will be allowed (must be equal to or
                 less than 10mg of prednisone/day).
    
              -  Has a known history of active TB (bacillus tuberculosis).
    
              -  Hypersensitivity to pembrolizumab or any of its excipients.
    
              -  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 radiation therapy
                 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.
    
                   -  Note: subjects with ≤ grade 2 neuropathy are an exception to this criterion and
                      may qualify for the 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.
    
              -  Has a known additional malignancy that is progressing or requires active treatment;
                 exceptions include basal cell carcinoma of the skin that has undergone potentially
                 curative therapy or in situ cervical cancer. Asymptomatic CLL, not requiring
                 intervention will be included as long as patients meet routine laboratory parameters
                 of the study as outlined above. In addition, patients who have undergone curative
                 bone marrow transplant and currently not requiring immunosuppression, will be allowed
                 on study.
    
              -  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.
    
              -  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 current
                 pneumonitis.
    
              -  Has an active infection requiring systemic therapy; exception HIV on antiretrovirals
                 with negative viral load.
    
              -  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-programmed cell death (PD)-1, anti-
                 programmed cell death 1 ligand (PD-L)1, or anti-PD-L2 agent.
    
              -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
                 hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
                 detected).
    
              -  Has received a live vaccine within 30 days of planned start of study therapy.
                 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.
    
              -  cSCC that is curable via radiation or surgery; palliative radiation is allowed as
                 long as measurable disease outside radiation field is present for study.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Response rate of pembrolizumab
    Time Frame:Up to 1 year after treatment discontinuation
    Safety Issue:
    Description:Will be estimated as percentage and 95% confidence interval will be constructed assuming a binomial distribution.

    Secondary Outcome Measures

    Measure:Overall survival
    Time Frame:Up to 1 year after treatment discontinuation
    Safety Issue:
    Description:Will be estimated with Kaplan Meier method and compared between different groups using Logrank test. Cox proportional model will be further employed to assess the treatment effect on survival with and without adjusting for other factors.
    Measure:Progression-free survival
    Time Frame:Up to 6 months after treatment discontinuation
    Safety Issue:
    Description:Will be estimated with Kaplan Meier method and compared between different groups using Logrank test. Cox proportional model will be further employed to assess the treatment effect on survival with and without adjusting for other factors.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Emory University

    Last Updated

    February 8, 2017