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

• ClinicalTrials.gov Identifier: NCT03914794
• Recruitment Status: Recruiting
• First Posted: April 16, 2019
• Last Update Posted: October 6, 2020
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Incyte Corporation
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

• First Submitted Date: April 11, 2019
• First Posted Date: April 16, 2019
• Last Update Posted Date: October 6, 2020
• Actual Study Start Date: October 2, 2020
• Estimated Primary Completion Date: May 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2019)

Complete response rate of pemigatinib therapy [ Time Frame: 6 weeks ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 11, 2019)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: Pemigatinib

Participants will take Pemigatinib once daily on days 1 through 28 of each cycle prior to standard of care TURBT.

Other Names:

• INCB054828
• FGFR inhibitor INCB054828

Study Arms

Experimental: Treatment: Pemigatinib

Patients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).

Intervention: Drug: Pemigatinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 11, 2019): 43
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2023
• Estimated Primary Completion Date: May 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Zak Zak; 410-502-4910; rzak5@jh.edu

Contact: Rana Sullivan; 410-614-6337; tomalra@jhmi.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03914794
• Other Study ID Numbers: J18158; IRB00194271 ( Other Identifier: JHM IRB )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Incyte Corporation

Investigators

• Principal Investigator: Noah M Hahn, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: October 2020