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

Bladder Cancer Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03914794
• Other study ID #: J18158
• Secondary ID: IRB00194271
• Status: Recruiting
• Phase: Phase 2
• Start date: October 2, 2020
• Est. completion date: May 2025

Study information

• Verified date: April 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Amber Michalik, BA
• Phone: 667-306-8336
• Email: amichal2[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 43
• Est. completion date: May 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• NMIBC
• Non-Muscle Invasive Bladder Cancer
• Recurrence
• Urinary Bladder Neoplasms
• 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.

Locations

Country	Name	City	State
United States	Midlantic Urology	Bala-Cynwyd	Pennsylvania
United States	Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Keystone Urology	Lancaster	Pennsylvania
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Associated Medical Professionals Urology	Syracuse	New York
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

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