Clinical Trials /

MK-3475/BCG in High Risk Superficial Bladder Cancer

NCT02324582

Description:

This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment for patients, 18 years or older, with high risk superficial bladder cancer (cancer not yet involving the muscle of the bladder wall) who have had removal of their bladder tumor. Patients will be enrolled to a single treatment group of a fixed dose of MK 3475 and BCG.

Related Conditions:
  • Bladder Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MK-3475/BCG in High Risk Superficial Bladder Cancer
  • Official Title: Phase I Study of MK-3475 in Combination With BCG for Patients With High Risk Superficial Bladder Cancer

Clinical Trial IDs

  • ORG STUDY ID: AL-SIUSOM-14-006
  • NCT ID: NCT02324582

Conditions

  • Bladder Cancer

Interventions

DrugSynonymsArms
Intravenous MK-3475/ Intravesical BCGpembrolizumabIntravenous MK-3475/ Intravesical BCG

Purpose

This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment for patients, 18 years or older, with high risk superficial bladder cancer (cancer not yet involving the muscle of the bladder wall) who have had removal of their bladder tumor. Patients will be enrolled to a single treatment group of a fixed dose of MK 3475 and BCG.

Detailed Description

      Bladder cancer is the fifth most common cancer in the United States. This is a single center
      Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused
      BCG treatment. The study will determine the safety of administering MK-3475 at a fixed dose
      every three weeks in conjunction with intravesicular BCG treatment in non-muscle invasive
      bladder cancer patients who had recurrence after two courses of induction (6 doses)
      intravesical therapy (two BCG courses, or one BCG course and one other approved intravesical
      therapies) administered within 12 months, or after one induction (6 doses) and one
      maintenance (3 doses) intrevesical therapy (BCG). Subjects will have confirmation of bladder
      cancer non-invasive to the muscle. Approximately 20 subjects will be screened to treat 15
      eligible subjects with high risk superficial bladder cancer who have had transurethral
      resection of their bladder tumor.

      The rationale for the use of the indicated dose of TICE® BCG is based upon FDA approved and
      commercially provided package insert/ instructions for use of the product. BCG installation
      has been used to treat non-muscle-invasive bladder cancer for more than 30 years. It is one
      of the most successful biotherapies for cancer in use. Despite long clinical experience with
      BCG, the mechanism of its therapeutic effect is still under investigation.

      The first 3 subjects will be treated at a dose of 100 mg MK-3475 to ensure safety for the
      combination. If no safety or efficacy issues are present, dosing will be escalated to 200 mg
      MK-3475 every 3 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Intravenous MK-3475/ Intravesical BCGExperimental3 subjects will be treated at a dose of 100 mg MK-3475 at 100 mg every 3 weeks (Q3W) intravenously (IV) for 6 doses and 1 vial intravesicular BCG suspended in 50 ml preservative-free saline once per week of 6 weekly doses 12 subjects will be treated at a dose of 200 mg MK-3475 at 100 mg every 3 weeks (Q3W) intravenously (IV) for 6 doses and 1 vial intravesicular BCG suspended in 50 ml preservative-free saline once per week of 6 weekly doses
  • Intravenous MK-3475/ Intravesical BCG

Eligibility Criteria

        Inclusion Criteria:

        1.Willing and able to provide written informed consent/assent.

        2.18 years of age.

        3.Have pathologically documented high grade transitional cell superficial bladder cancer
        (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the
        bladder at time of initial resection for recurrent/persistent high risk transitional cell
        superficial bladder cancer.

        4.Recurrent/persistent disease despite 2 Induction Intravesical Therapy Courses given
        within 12 months (with BCG being one of them), or despite one induction BCG treatment in
        addition to at least one maintenance course of BCG 5.Have provided tissue from an archival
        tissue sample or newly obtained core or excisional biopsy of a tumor lesion.

        6.ECOG performance status of 0-2. 7.Demonstrate adequate organ function 8.Female subject of
        childbearing potential should have a negative urine or serum pregnancy.

        9.Female subjects of childbearing potential should be willing to use 2 methods of birth
        control or abstain from heterosexual activity for the course of the study through 120 days
        after the last dose of study medication 10.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:

          1. Currently has active or progressive metastatic disease.

          2. Currently participating in or has participated in a study of an investigational agent
             or using an investigational device within 4 weeks of the first dose of treatment.

          3. 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.

          4. Prior monoclonal antibody 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.

          5. Prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for
             bladder cancer.

          6. If subject received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy.

          7. Known additional malignancy that is progressing or requires active treatment.

          8. Active autoimmune disease that has required systemic treatment in past 2 years.

          9. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

         10. Active infection, including a concurrent febrile illness, requiring systemic therapy.

         11. 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.

         12. Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

         13. 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 4 months after the last dose of trial treatment.

         14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways) including anti-CD40 and anti-OX40 antibodies.

         15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         16. Has known active Hepatitis B (e.g., HBs Ag reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         17. Has known active tuberculosis. Subjects will not be specifically tested for the study;
             however, subjects that are tested within 28 days of beginning study or while on study
             and test positive with the PPD test before treatment should have active tuberculosis
             ruled out before therapy begins for their superficial bladder cancer.

         18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

         19. Has an active urinary tract infection, gross hematuria, or known broken mucosal
             barrier of the bladder.

         20. Less than 14 days post bladder biopsy, TUR, or traumatic catheterization.

         21. Evidence of muscle invasive bladder cancer, or transitional cell carcinoma of the
             upper urinary tract
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:safety (Grade and quantity of adverse events)
Time Frame:change from baseline to 23 weeks
Safety Issue:
Description:Grade and quantity of adverse events

Secondary Outcome Measures

Measure:Complete Response Rate (cytoscopy)
Time Frame:change from baseline to 19 weeks; 3, 12, and 24 months post treatment completion
Safety Issue:
Description:cytoscopy; urine cytology
Measure:Change in Quality of Life
Time Frame:change from baseline to 10 weeks, 19 weeks and 3, 12, and 24 months post-Week 19 cystectomy
Safety Issue:
Description:American Urologic Association Symptoms Index (AUA IPSS)
Measure:Change in Quality of Life
Time Frame:change from baseline to 10 weeks, 19 weeks and 3, 12, and 24 months post-Week 19 cystectomy
Safety Issue:
Description:Quality of Life (QOL) question

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southern Illinois University

Trial Keywords

  • Urinary Bladder Neoplasms
  • Mycobacterium bovis
  • Programmed Cell Death 1 Receptor
  • pembrolizumab

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