Clinical Trials /

A Study of Erdafitinib in People With Recurrent Non-Invasive Bladder Cancer

NCT04917809

Description:

The purpose of this study is to find out whether erdafitinib is an effective treatment for FGFR3-altered non-muscle invasive bladder cancer/NMIBC between the time that a recurrent tumor is identified and a TURBT (transurethral resection of a bladder tumor) or biopsy procedure is performed to remove it.

Related Conditions:
  • Non-Muscle Invasive Bladder Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Erdafitinib in People With Recurrent Non-Invasive Bladder Cancer
  • Official Title: A Phase 2 "Window of Opportunity" Trial of Targeted Therapy With Erdafitinib in Patients With Recurrent FGFR3-Altered Non-Muscle Invasive Bladder Cancer

Clinical Trial IDs

  • ORG STUDY ID: 21-166
  • NCT ID: NCT04917809

Conditions

  • Bladder Cancer
  • Recurrent Bladder Cancer
  • FGFR3 Gene Mutation

Interventions

DrugSynonymsArms
ErdafitinibParticipants with FGFR3-mutant or -fusion noninvasive bladder tumors

Purpose

The purpose of this study is to find out whether erdafitinib is an effective treatment for FGFR3-altered non-muscle invasive bladder cancer/NMIBC between the time that a recurrent tumor is identified and a TURBT (transurethral resection of a bladder tumor) or biopsy procedure is performed to remove it.

Trial Arms

NameTypeDescriptionInterventions
Participants with FGFR3-mutant or -fusion noninvasive bladder tumorsExperimental25 participants with FGFR3-mutant or -fusion noninvasive bladder tumors will be accrued.
  • Erdafitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent for the trial.

          -  Documentation on MSK-IMPACT of an oncogenic FGFR3 mutation (R248C, S249C, G370C,
             Y373C, etc.) or FGFR3 gene fusion with compelling clinical or biologic evidence in the
             OncoKB Precision Oncology Knowledge Base (https://oncokb.org/) from either archival
             NMIBC tumor tissue or recent TURBT/biopsy specimen of current tumor tissue.

          -  Any recurrence of noninvasive-appearing papillary tumor(s) (clinical Ta disease) after
             at least 1 previous course of intravesical therapy with either:

               -  (1) a history of a high-grade Ta tumor -OR-

               -  (2) a history of low-grade T1 tumor -OR-

               -  (3) low-grade Ta tumor with the new recurrent tumor demonstrating at least 1
                  additional "unfavorable" risk factor for future recurrence:

          -  Multiple tumors

          -  Tumor size ≥3 cm

          -  Early recurrence ≤12 months from last treatment

          -  Frequent recurrences ≥1 per year

             ° Given the frequent shortages of BCG, a prior course of therapy with either BCG
             therapy or intravesical chemotherapy (mitomycin, gemcitabine, etc.) is acceptable. All
             prior treatments for NMIBC will recorded and described.

          -  Ages 18 or older.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          -  Adequate bone marrow, liver, and renal function:

             ° Bone marrow function:

          -  Absolute neutrophil count (ANC) ≥1,000/mm3

          -  Platelet count ≥75,000/mm3

          -  Hemoglobin ≥8.0 g/dL

             ° Liver function:

          -  Total bilirubin ≤1.5 x ULN

          -  Alanine aminotransferase (ALT) ≤2.5 x ULN

          -  Aspartate aminotransferase (AST) ≤2.5x ULN

             ° Renal function:

          -  estimated glomerular filtration rate >30 mL/min/1.73m2 calculated using the
             modification of diet in renal disease equation or CKD-EPI formula

          -  Serum Phosphate level <ULN prior to starting treatment

          -  Able to swallow pills

          -  Female subjects of childbearing potential should be on birth control, have male
             partners using a condom during intercourse, be surgically sterile, or abstain from
             heterosexual activity for the course of the study through 120 days after the last dose
             of the study therapy. Subjects of childbearing potential are those who have not been
             surgically sterilized or have not been free from menses for >1 year.

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.
             While taking the study drug and for three months after the last dose of the study
             drug, sexually active males must use a condom during intercourse. They should not
             father a child during this period. Men who have undergone vasectomy are also required
             to use a condom during intercourse, to prevent delivery of the drug via seminal fluid.

        Exclusion Criteria:

          -  Impaired decision-making capacity

          -  Pregnant (positive pregnancy test) or lactating.

          -  History of or currently being treated for muscle-invasive (i.e., stage T2 or higher)
             or metastatic urothelial cell carcinoma.

          -  Evidence of concurrent extravesical (i.e., urethra, ureter, or renal pelvis)
             urothelial cell carcinoma.

          -  Evidence of carcinoma in situ only disease (stage Tis) or concurrent carcinoma in
             situ.

          -  Patients who meet the definition BCG-unresponsive NMIBC as defined as:

               -  HGT1 within 3 months after an induction BCG course (received ≥5 of 6 doses)

               -  Persistent or recurrent high-grade NMIBC (Tis, Ta, T1) within 6 months of ≥5 of 6
                  doses of induction BCG therapy and ≥2 of 3 doses of maintenance BCG therapy

          -  History of or currently being treated for or scheduled to have radiation treatment for
             bladder cancer; prior radiation therapy for prostate cancer or another nonbladder
             cancer is allowed.

          -  Prior systemic chemotherapy, targeted therapy, or treatment with an investigational
             anticancer agent within 30 days or ≤5 half-lives of the agent (whichever is longer)
             before the first dose of erdafitinib.

          -  Prior immunotherapy within 30 days before the first dose of erdafitinib and/or has an
             ongoing grade ≥ 2 immunotherapy-related toxicity.

          -  Unstable angina, myocardial infarction within the preceding 3 months, or known New
             York Heart Association class II-IV congestive heart failure.

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Cerebrovascular accident or transient ischemic attack within the preceding 3 months.

          -  Prior treatment with a selective FGFR inhibitor (including but not limited to AZD4547,
             BGJ398, BAY1163877, and LY2874455).

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of oral erdafitinib (e.g., ulcerative diseases,
             uncontrolled nausea, vomiting, diarrhea, and malabsorption syndrome).

          -  Current evidence of endocrine alterations of calcium/phosphate homeostasis (e.g.,
             parathyroid disorders, history of parathyroidectomy, tumor lysis, and tumoral
             calcinosis).

          -  Use of medications that increase serum levels of phosphorus and/or calcium (e.g.,
             calcium, phosphate, vitamin D, and parathyroid hormone). Patients on these medications
             can participate in the study if they are able to discontinue them while receiving
             treatment with erdafitinib.

          -  Use of medications that are known strong or moderate inhibitors or inducers of CYP3A4
             or CYP2C9 (A comprehensive list is included in the Appendix: Drugs Classified as
             Strong or Moderate In Vivo Inhibitors and Inducers of CYP3A4/2C9 Enzymes). Patients on
             these medications can participate in the study if they are able to discontinue them
             prior to starting treatment with erdafitinib.

          -  Current evidence of corneal or retinal disorder/keratopathy, including but not limited
             to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and/or
             keratoconjunctivitis, confirmed by ophthalmologic examination.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:3 weeks after first study treatment
Safety Issue:
Description:The primary endpoint of this trial is the objective response rate at the time of TURBT/biopsy (defined as the proportion of patients achieving a complete or partial pathologic response by cytologic examination, cystoscopic examination, and biopsy) following treatment with erdafitinib. A complete response is defined as the absence of tumor on TURBT/biopsy, with a negative urinary cytologic result; a partial response is defined as a decrease of at least 50% in the size of the target tumor(s), on the basis of modified RECIST 1.1 criteria (RECIT-BLADDER).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Non-Muscle Invasive Bladder Cancer
  • NMIBC
  • Erdafitinib
  • FGFR3
  • 21-166
  • Memorial Sloan Kettering Cancer Center

Last Updated

June 8, 2021