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A Study of Pemigatinib in Non-muscle Invasive Bladder Cancer Patients With Recurrent Low- or Intermediate-Risk Tumors

NCT03914794

Description:

This phase II trial studies how well Pemigatinib (an orally administered inhibitor of fibroblast growth factor receptors 1, 2, and 3) works in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Participants will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).

Related Conditions:
  • Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Pemigatinib in Non-muscle Invasive Bladder Cancer Patients With Recurrent Low- or Intermediate-Risk Tumors
  • Official Title: Phase 2 Window of Opportunity Study of Pemigatinib in Non-muscle Invasive Bladder Cancer Patients With Recurrent Low- or Intermediate-Risk Tumors

Clinical Trial IDs

  • ORG STUDY ID: J18158
  • SECONDARY ID: IRB00194271
  • NCT ID: NCT03914794

Conditions

  • Bladder Cancer
  • NMIBC
  • Non-Muscle Invasive Bladder Cancer
  • Urothelial Carcinoma Recurrent

Interventions

DrugSynonymsArms
PemigatinibINCB054828, FGFR inhibitor INCB054828Treatment: Pemigatinib

Purpose

This phase II trial studies how well Pemigatinib (an orally administered inhibitor of fibroblast growth factor receptors 1, 2, and 3) works in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Participants will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).

Detailed Description

      It is a single-arm phase 2 window of opportunity study to assess the antineoplastic activity
      of pemigatinib in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors
      and a prior history of low- or intermediate-risk NMIBC tumors. Enrolled patients will receive
      pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor
      (TURBT). The primary endpoint will be complete response rate as determined at TURBT.
      Secondary endpoints will include safety profile, associations between complete response rate
      and tumor mutation/fusion status (e.g. FGFR3 specifically, others will also be examined) and
      NMIBC risk group (low- vs. intermediate-risk), and assessment of pemigatinib post-treatment
      urothelial tissue concentrations. The study will be conducted at 4-5 high volume bladder
      cancer institutions within the US and managed through the Johns Hopkins Sidney Kimmel
      Comprehensive Cancer Center clinical research office.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment: PemigatinibExperimentalPatients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).
  • Pemigatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Prior histologically confirmed low- or intermediate-risk non-muscle invasive
             urothelial carcinoma of the bladder (NMIBC) defined according to the following
             characteristics:

               -  Low Risk

                    -  Initial tumor with all of the following:

                    -  Solitary tumor

                    -  Ta tumor

                    -  Low-grade

                    -  <3 cm

                    -  No CIS

               -  Intermediate Risk

                  --- All tumors not defined in the two adjacent categories (between the category
                  of low- and high-risk)

               -  High Risk

                    -  T1 tumor

                    -  High-grade

                    -  CIS

                    -  Multiple and recurrent and large (>3 cm) Ta low-grade tumors (all conditions
                       must be met for this point on Ta low-grade tumors)

          -  Documented tumor recurrence as noted in standard of care follow up cystoscopy.

          -  ECOG (WHO) performance status 0-2

          -  Age ≥ 18 years old

          -  Patients must have the following laboratory values:

               -  White blood cell count (WBC) > 3.0 K/mm3

               -  Absolute neutrophil count (ANC) ≥ 1.5 K/mm3

               -  Platelets ≥ 100 K/mm3

               -  Hemoglobin (Hgb) ≥ 9 g/dL

               -  Serum total bilirubin: ≤ 1.5 x ULN

               -  ALT and AST ≤ 3.0 x ULN

               -  Serum calcium < ULN

               -  Serum phosphate < ULN

               -  Serum creatinine ≤ 1.5 x ULN or serum creatinine > 1.5 - 3 x ULN if calculated
                  creatinine clearance (CrCl) is ≥ 30 mL/min using the modified Cockcroft-Gault
                  equation

          -  Patients who give a written informed consent obtained according to local guidelines

        Exclusion Criteria:

          -  Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive
             urothelial carcinoma.

          -  Patients with high grade urothelial carcinoma on their most recent urine cytology.

          -  Patients with another active second malignancy other than non-melanoma skin cancers
             and biochemical relapsed prostate cancer. (Patients that have completed all necessary
             therapy and are considered to be at less than 30% risk of relapse are not considered
             to have an active second malignancy and are eligible for enrollment.)

          -  Patients who have received the last administration of an anti-cancer therapy including
             chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting
             study drug, or who have not recovered from the side effects of such therapy

          -  Patients who have received prior selective fibroblast growth factor receptor targeting
             agents (i.e. pemigatinib, dovitinib, BGJ398, AZD4547, JNJ-42756493, etc.).

          -  Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have
             not recovered from radiotherapy toxicities

          -  Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or
             intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting
             study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous
             biopsies or placement of vascular access device ≤ 1 week prior to starting study drug,
             or who have not recovered from side effects of such procedure or injury
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete response rate of pemigatinib therapy
Time Frame:6 weeks
Safety Issue:
Description:The number of participants with a complete response to pemigatinib therapy. Tumor complete response is defined as the complete absence of any stage bladder tumor on post-treatment Transurethral Resection of a Bladder Tumor (TURBT) and no evidence of recurrent urothelial carcinoma on post-treatment urine cytology.

Secondary Outcome Measures

Measure:Characterize the safety profile of pemigatinib therapy
Time Frame:4 years
Safety Issue:
Description:Number of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 toxicities
Measure:Number of Participants with Complete Response and FGFR3 Mutational Status
Time Frame:Up to 4 weeks
Safety Issue:
Description:
Measure:Number of Participants with Non-Muscle Invasive Bladder Cancer (NMIBC) and Complete Response
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with complete response rate and baseline NMIBC risk group (low- vs. intermediate-risk)
Measure:Maximal concentration (Cmax, nmol/L) of pemigatinib in urothelial tissue at post-treatment TURBT
Time Frame:Up to 4 weeks
Safety Issue:
Description:
Measure:Relapse Free Survival (RFS) at 6 months
Time Frame:6 months
Safety Issue:
Description:Number of months from achieving a complete response at initial post-treatment TURBT until relapse.
Measure:Relapse Free Survival (RFS) at 12 months
Time Frame:12 months
Safety Issue:
Description:Number of months from achieving a complete response at initial post-treatment TURBT until relapse.
Measure:Relapse Free Survival (RFS) at 24 months
Time Frame:24 months
Safety Issue:
Description:Number of months from achieving a complete response at initial post-treatment TURBT until relapse.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Bladder Cancer
  • Non Muscle Invasive Bladder Cancer
  • Non-Muscle Invasive Bladder Cancer (NMIBC)
  • NMIBC
  • Urothelial Carcinoma
  • Urothelial Cancer
  • Urinary Bladder Neoplasm
  • Bladder Neoplasm
  • Fibroblast inhibitors
  • Pemigatinib
  • FGFR inhibitor

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