Clinical Trials /

Trial of Pembrolizumab for Advanced Penile Squamous Cell Carcinoma

NCT02837042

Description:

Penile squamous cell carcinoma (PSCC) is relatively rare but exhibits higher incidences in less developed countries. PSCC is a highly aggressive malignancy characterized by early spread. Pembrolizumab has recently been FDA-approved for the treatment of melanoma but will serve as the investigational agent for this penile cancer study.

Related Conditions:
  • Squamous Cell Carcinoma of the Penis
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Pembrolizumab for Advanced Penile Squamous Cell Carcinoma
  • Official Title: Phase II Trial of Pembrolizumab for Advanced Penile Squamous Cell Carcinoma Following Previous Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: F160426013 (UAB 15107)
  • NCT ID: NCT02837042

Conditions

  • Penile Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPembrolizumab 200 mg

Purpose

Penile squamous cell carcinoma (PSCC) is relatively rare but exhibits higher incidences in less developed countries. PSCC is a highly aggressive malignancy characterized by early spread. Pembrolizumab has recently been FDA-approved for the treatment of melanoma but will serve as the investigational agent for this penile cancer study.

Detailed Description

      This is a multicenter trial to evaluate Pembrolizumab for patients with advanced penile
      squamous cell carcinoma following prior chemotherapy. Participating institutions are the
      University of Alabama at Birmingham (coordinating center), M.D. Anderson Cancer Center,
      University of Michigan, University of Minnesota, and Emory University. Patients will receive
      intravenous Pembrolizumab every 3 weeks and undergo a clinical exam. Radiographic scans will
      be done at baseline and every 9 weeks. Therapy will continue until disease progression or
      there are intolerable toxicities.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab 200 mgExperimentalOnce eligibility is confirmed, the patient will start treatment cycles with Pembrolizumab at 200 mg given intravenously on the first day of each cycle. Each cycle corresponds to a duration of 3 weeks.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Locally advanced unresectable or metastatic stage 4 (i.e. T4 or N3 or M1) PSCC

          2. Radiologic evidence for progressive disease after ≥1 prior chemotherapy regimen

          3. Be at least 18 years of age on day of signing informed consent.

          4. Have measurable disease based on RECIST 1.1.

          5. Have a performance status of 0-2 on the ECOG (Eastern Cooperative Oncology Group)
             Performance Scale.

          6. Demonstrate adequate organ function with all screening labs being performed within 14
             days of treatment initiation.

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥100,000/mcL

               -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin
                  dependency (within 7 days of assessment)

               -  Serum creatinine ≤1.5 X upper limit of normal (ULN); alternately measured or
                  calculated creatinine clearance ≥30 mL/min with creatinine levels >1.5 X
                  institutional ULN (GFR can also be used in place of creatinine or CrCl)

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

               -  AST (SGOT) and ALT (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 PTT is within
                  therapeutic range of intended use of anticoagulants

               -  Activated Partial Thromboplastin Time (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

          7. 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

          8. Formalin-fixed paraffin embedded (FFPE) tumor tissue from previous biopsy is
             requested, but not mandatory.

          9. Be willing and able to provide written informed consent/assent for the trial.

        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 systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of
             trial treatment.

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

          6. 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.

          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 (e.g. 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, or any evidence of active, non-infectious 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 expecting to 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 known active Tuberculosis infection.

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

Primary Outcome Measures

Measure:Objective tumor response rate
Time Frame:Baseline up to two years
Safety Issue:
Description:The response rate will be evaluated every 3 weeks using the criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in addition to immune related criteria based on patterns of response.

Secondary Outcome Measures

Measure:Duration of response and stable disease
Time Frame:From the first treatment up to two years
Safety Issue:
Description:Objective tumor response rates will be accumulated until disease progression by immune related criteria, death, or intolerable toxicities.
Measure:Progression-free survival
Time Frame:Baseline up to two years
Safety Issue:
Description:The duration of time from the start of treatment to the first documentation of tumor progression.
Measure:Overall survival
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Safety Issue:
Description:Length of subject survival after starting study treatment
Measure:Number of adverse events
Time Frame:Baseline up to two years
Safety Issue:
Description:Adverse events reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Alabama at Birmingham

Trial Keywords

  • penile cancer
  • Pembrolizumab
  • penile squamous cell carcinoma
  • squamous cell cancer

Last Updated

April 17, 2017