Pemigatinib treatment for recurrent low- or intermediate-risk bladder cancer

Phase 2 Window of Opportunity Study of Pemigatinib in Non-muscle Invasive Bladder Cancer Patients With Recurrent Low- or Intermediate-Risk Tumors

This study is testing if a new oral medication called Pemigatinib can help people with recurrent low- or intermediate-risk bladder cancer before they have surgery to remove their tumors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: pemigatinib, dovitinib, chemotherapy, immunotherapy
• Locations: 6 sites (Washington, District of Columbia and 5 other locations)
• Trial ID: NCT03914794 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of Pemigatinib, an oral inhibitor targeting fibroblast growth factor receptors, in patients with recurrent non-muscle invasive bladder cancer (NMIBC) who have a history of low- or intermediate-risk tumors. Participants will receive Pemigatinib for 4-6 weeks before undergoing standard transurethral resection of bladder tumor (TURBT). The primary goal is to assess the complete response rate at TURBT, while secondary goals include evaluating safety and the relationship between treatment response and tumor characteristics. The study will be conducted at several high-volume bladder cancer institutions in the US.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a documented history of low- or intermediate-risk NMIBC and recurrent tumors.

Not a fit: Patients with high-risk NMIBC or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with recurrent NMIBC by enhancing tumor response prior to surgical intervention.

How similar studies have performed: Other studies have shown promising results with FGFR inhibitors in bladder cancer, indicating potential for success with this approach.

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

Where this trial is running

Washington, District of Columbia and 5 other locations

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

Study contacts

• Principal investigator: Noah M Hahn, MD — Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study coordinator: Amber Michalik, BA

Conditions Bladder Cancer; NMIBC; Non-Muscle Invasive Bladder Cancer; Urothelial Carcinoma Recurrent; Non Muscle Invasive Bladder Cancer; Urothelial Carcinoma; Urothelial Cancer; Urinary Bladder Neoplasm