Clinical trial NCT03914794: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Bladder Cancer
NMIBC
Non-Muscle Invasive Bladder Cancer
Urothelial Carcinoma Recurrent
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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2019-04-16
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete response rate of pemigatinib therapy
timeFrame: 6 weeks
Secondary outcomes:
measure: Characterize the safety profile of pemigatinib therapy
timeFrame: 4 years
measure: Number of Participants with Complete Response and FGFR3 Mutational Status
timeFrame: Up to 4 weeks
measure: Number of Participants with Non-Muscle Invasive Bladder Cancer (NMIBC) and Complete Response
timeFrame: Up to 4 years
measure: Maximal concentration (Cmax, nmol/L) of pemigatinib in urothelial tissue at post-treatment TURBT
timeFrame: Up to 4 weeks
measure: Relapse Free Survival (RFS) at 6 months
timeFrame: 6 months
measure: Relapse Free Survival (RFS) at 12 months
timeFrame: 12 months
measure: Relapse Free Survival (RFS) at 24 months
timeFrame: 24 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Syracuse
country: United States
facility: Associated Medical Professionals Urology
state: New York
city: Bala-Cynwyd
country: United States
facility: Midlantic Urology
state: Pennsylvania
city: Lancaster
country: United States
facility: Keystone Urology
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Noah M Hahn, MD
role: PRINCIPAL_INVESTIGATOR
References: