Description:
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).
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
J18158
- SECONDARY ID:
IRB00194271
- NCT ID:
NCT03914794
Conditions
- Bladder Cancer
- NMIBC
- Non-Muscle Invasive Bladder Cancer
- Urothelial Carcinoma Recurrent
Interventions
Drug | Synonyms | Arms |
---|
Pemigatinib | INCB054828, FGFR inhibitor INCB054828 | Treatment: Pemigatinib |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment: Pemigatinib | Experimental | Patients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT). | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Complete response rate of pemigatinib therapy |
Time Frame: | 6 weeks |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Characterize the safety profile of pemigatinib therapy |
Time Frame: | 4 years |
Safety Issue: | |
Description: | Number of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 toxicities |
Measure: | Number of Participants with Complete Response and FGFR3 Mutational Status |
Time Frame: | Up to 4 weeks |
Safety Issue: | |
Description: | |
Measure: | Number of Participants with Non-Muscle Invasive Bladder Cancer (NMIBC) and Complete Response |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | Number of participants with complete response rate and baseline NMIBC risk group (low- vs. intermediate-risk) |
Measure: | Maximal concentration (Cmax, nmol/L) of pemigatinib in urothelial tissue at post-treatment TURBT |
Time Frame: | Up to 4 weeks |
Safety Issue: | |
Description: | |
Measure: | Relapse Free Survival (RFS) at 6 months |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Number of months from achieving a complete response at initial post-treatment TURBT until relapse. |
Measure: | Relapse Free Survival (RFS) at 12 months |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Number of months from achieving a complete response at initial post-treatment TURBT until relapse. |
Measure: | Relapse Free Survival (RFS) at 24 months |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Number of months from achieving a complete response at initial post-treatment TURBT until relapse. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial 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
Last Updated
October 6, 2020