Clinical Trials /

Pembrolizumab in Combination With BCG After Ablation in Patients With UUTTCC Without Nephroureterectomy

NCT03345134

Description:

PURPOSE: This study is being conducted to test the safety of the study drug Pembrolizumab, also known as MK-3475, at different dose levels in combination with the current therapy, (BCG), for superficial upper urinary tract transitional cell carcinoma. We want to find out what effects, good and/or bad, it has on upper urinary transitional cell carcinoma OBJECTIVE: To determine the safety of administering MK-3475 at a fixed dose of 200 mg every three weeks in conjunction with intrapelvic BCG treatment in high risk superficial UUTTCC patients who are unfit or unwilling to be treated with radical nephroureterectomy. STUDY DESIGN: Open-label, single center, Phase II, treatment trial TREATMENT: BCG- BCG treatment could be delivered both through a retrograde ureteral catheter placed under fluoroscopic control or through an antegrade nephrostomy tube placed by interventional radiology. Treatment will be once a week for 6 weeks. BCG treatment will begin on Day 1 of Week 7. Depending on patient's response, they may have additional treatments beyond the 6 scheduled, but they will be outside of the patient's participation in this study. Pembrolizumab will be given through an intravenous needle once every 21 days (one cycle) for a total of 6 cycles. It will take 30 minutes for the infusion of the study drug. Pembrolizumab will be given on Day 1 of weeks 1, 4, 7, 10, 13, and 16 while BCG will be given on Day 1 of weeks 7-12. PROCEDURES: Following informed consent, prescreening and screening procedures will be performed, which will include medical history review, baseline chest x ray and EKG, ureteroscopy and pulmonary function tests for final eligibility status. Once subject is eligible, they will undergo physical exams (every 3 weeks), vital signs and weight (each study visit), adverse event monitoring (each study visit), ECGs (screening visit), bloodwork (at screening and then every 3 weeks), urinalysis at selected study visits, and concomitant medication review (each study visit), and questionnaires (selected study visits). After subject has completed week 19, they will have a study discontinuation visit, followed by a 30 day follow up visit. The subject will then be followed at 3, 6, 9, 12, 18 and 24 months post treatment where vital status will be determined as well as disease recurrence status. Ureteroscopy will be performed as standard of care but will be considered measures for efficacy. Biopsy will be performed as clinically indicated.

Related Conditions:
  • Renal Pelvis and Ureter Urothelial Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Combination With BCG After Ablation in Patients With UUTTCC Without Nephroureterectomy
  • Official Title: Phase II Study of Pembrolizumab in Combination With BCG After Endoscopic Ablation for Patients With High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma Unfit or Unwilling to be Treated With Nephroureterectomy

Clinical Trial IDs

  • ORG STUDY ID: HFHS 16-01
  • NCT ID: NCT03345134

Conditions

  • High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma
  • Endoscopic Surgical Procedure
  • Transitional Epithelial Cells

Interventions

DrugSynonymsArms
MK-3475 and BCGMK-3475 and BCG

Purpose

PURPOSE: This study is being conducted to test the safety of the study drug Pembrolizumab, also known as MK-3475, at different dose levels in combination with the current therapy, (BCG), for superficial upper urinary tract transitional cell carcinoma. We want to find out what effects, good and/or bad, it has on upper urinary transitional cell carcinoma OBJECTIVE: To determine the safety of administering MK-3475 at a fixed dose of 200 mg every three weeks in conjunction with intrapelvic BCG treatment in high risk superficial UUTTCC patients who are unfit or unwilling to be treated with radical nephroureterectomy. STUDY DESIGN: Open-label, single center, Phase II, treatment trial TREATMENT: BCG- BCG treatment could be delivered both through a retrograde ureteral catheter placed under fluoroscopic control or through an antegrade nephrostomy tube placed by interventional radiology. Treatment will be once a week for 6 weeks. BCG treatment will begin on Day 1 of Week 7. Depending on patient's response, they may have additional treatments beyond the 6 scheduled, but they will be outside of the patient's participation in this study. Pembrolizumab will be given through an intravenous needle once every 21 days (one cycle) for a total of 6 cycles. It will take 30 minutes for the infusion of the study drug. Pembrolizumab will be given on Day 1 of weeks 1, 4, 7, 10, 13, and 16 while BCG will be given on Day 1 of weeks 7-12. PROCEDURES: Following informed consent, prescreening and screening procedures will be performed, which will include medical history review, baseline chest x ray and EKG, ureteroscopy and pulmonary function tests for final eligibility status. Once subject is eligible, they will undergo physical exams (every 3 weeks), vital signs and weight (each study visit), adverse event monitoring (each study visit), ECGs (screening visit), bloodwork (at screening and then every 3 weeks), urinalysis at selected study visits, and concomitant medication review (each study visit), and questionnaires (selected study visits). After subject has completed week 19, they will have a study discontinuation visit, followed by a 30 day follow up visit. The subject will then be followed at 3, 6, 9, 12, 18 and 24 months post treatment where vital status will be determined as well as disease recurrence status. Ureteroscopy will be performed as standard of care but will be considered measures for efficacy. Biopsy will be performed as clinically indicated.

Trial Arms

NameTypeDescriptionInterventions
MK-3475 and BCGExperimentalSingle treatment group of high risk superficial upper urinary tract transitional cell carcinoma; combination treatment with MK-3475 and BCG
  • MK-3475 and BCG

Eligibility Criteria

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent for the trial.

          2. Be at least18 years of age on day of signing informed consent.

          3. Have pathologically documented high grade UUTTCC (CIS, Ta, T1) that could be
             completely ablated with ureteroscopy or through antegrade percutaneous access.

          4. Subject must also unwilling or unfit to undergo treatment with radical
             nephroureterectomy

          5. Have provided tissue from an archival tissue sample or newly obtained core or
             excisional biopsy of a tumor lesion. Tissue must be obtained from the most recent
             upper urinary tract biopsy.

          6. Have a performance status of 0-1 on the ECOG Performance Scale (Appendix A).

          7. Demonstrate adequate organ function, all screening labs should be performed within 28
             days of treatment initiation.

          8. Female subject of childbearing potential should have a negative urine or serum
             pregnancy test 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.

          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 (Reference Section 5.5.2). Subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year.

         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.

         11. Patients who received prior systemic chemotherapy, targeted small molecule therapy, or
             radiation therapy for UUTTCC are allowed into the study as long as there is confirmed
             recurrence of the disease after previous treatment and the patient is unwilling or
             unfit to undergo radical surgery.

        Exclusion Criteria:

          1. Currently has active or progressive metastatic disease. (Chest X-ray, Computerized
             Tomography [CT] urogram or Magnetic Resonance Imaging [MRI], and urogram are allowed
             to ascertain the superficial nature of the disease when indicated, but not required.
             If urogram protocol is not available or contrast allergy/poor renal function precludes
             such imaging, then non-contrast CT or MRI of the abdomen/pelvis within 90 days of
             study entry will suffice.)

          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 had a prior monoclonal antibody within 4 weeks before 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.

          4. Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation
             therapy for UUTTCC.

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

          6. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, localized prostate cancer with no recurrence after curative surgery or
             radiation, or in situ cervical cancer that has undergone potentially curative therapy.
             Lower urinary tract transitional cell carcinoma is also allowable on study as high
             risk transitional cell carcinoma is commonly multifocal, and intraluminal BCG therapy
             is also used for treatment of lower urinary tract lesions in a manner similar to that
             of UUTTCC.

          7. 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.

          8. Has history of (non-infectious) pneumonitis that required steroids, evidence of
             interstitial lung disease, or active , non-infectious pneumonitis.

          9. Has an active infection, including a concurrent febrile illness, requiring systemic
             therapy.

         10. 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.

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

         12. 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.

         13. 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.

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

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

         16. 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 renal pelvis cancer.

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

         18. Has an active urinary tract infection, gross hematuria, or known broken mucosal
             barrier of the renal pelvis.

         19. Less than 14 days post renal pelvis biopsy, TUR, or traumatic catheterization.

         20. Evidence of muscle invasive renal pelvis 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:Complete Response per ureteroscopy and pathological confirmation of tissue biopsy
Time Frame:At 19 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Complete Response per ureteroscopy and pathological confirmation of tissue biopsy
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shaheen Alanee

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