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

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ClinicalTrials.gov Identifier: NCT03914794

Recruitment Status : Recruiting

First Posted : April 16, 2019

Last Update Posted : December 3, 2019

See Contacts and Locations

Sponsor:

Collaborator:

Incyte Corporation

Information provided by (Responsible Party):

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

First Submitted Date ^ICMJE

April 11, 2019

First Posted Date ^ICMJE

April 16, 2019

Last Update Posted Date

December 3, 2019

Actual Study Start Date ^ICMJE

November 11, 2019

Estimated Primary Completion Date

May 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

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 ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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 ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

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

Intervention ^ICMJE

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 ^ICMJE

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

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

May 2023

Estimated Primary Completion Date

May 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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 ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Abby Asiama	410-955-1168	aasiama1@jhmi.edu
Contact: Rana Sullivan	410-614-6337	tomalra@jhmi.edu

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03914794

Other Study ID Numbers ^ICMJE

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 ^ICMJE

Plan to Share IPD:

Responsible Party

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Sponsor ^ICMJE

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators ^ICMJE

Incyte Corporation

Investigators ^ICMJE

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

December 2019

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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