- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04917809
A Study of Oral Erdafitinib in People With Recurrent Non-Invasive Bladder Cancer
A Phase 2 "Window of Opportunity" Trial of Targeted Therapy With Erdafitinib in Patients With Recurrent FGFR3-Altered Non-Muscle Invasive Bladder Cancer
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Gopakumar Iyer, MD
- Phone Number: 646-888-4737
- Email: iyerg@mskcc.org
Study Contact Backup
- Name: Eugene Pietzak, MD
- Phone Number: 646-422-4781
- Email: pietzake@mskcc.org
Study Locations
-
-
New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Recruiting
- Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
-
Contact:
- Eugene Pietzak, MD
- Phone Number: 646-422-4781
-
Middletown, New Jersey, United States, 07748
- Recruiting
- Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
-
Contact:
- Eugene Pietzak, MD
- Phone Number: 646-422-4781
-
Montvale, New Jersey, United States, 07645
- Recruiting
- Memorial Sloan Kettering Bergen (Limited Protocol Activities)
-
Contact:
- Eugene Pietzak, MD
- Phone Number: 646-422-4781
-
-
New York
-
Commack, New York, United States, 11725
- Recruiting
- Memorial Sloan Kettering Commack (Limited Protocol Activities)
-
Contact:
- Eugene Pietzak, PhD
- Phone Number: 646-422-4781
-
Harrison, New York, United States, 10604
- Recruiting
- Memorial Sloan Kettering Westchester (Limited Protocol Activities)
-
Contact:
- Eugene Pietzak, MD
- Phone Number: 646-422-4781
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center (All protocol activities)
-
Contact:
- Eugene Pietzak, MD
- Phone Number: 646-422-4781
-
Uniondale, New York, United States, 11553
- Recruiting
- Memorial Sloan Kettering Nassau (Limited protocol activities)
-
Contact:
- Eugene Pietzak, MD
- Phone Number: 646-422-4781
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participants must have NMIBC that has come back after prior treatment (instillations of BCG or chemotherapy into the bladder).
- Genetic testing of the participant's prior or recurrent NMIBC tumor will be performed to confirm the presence of an FGFR3 mutation
- Patients must be able to walk and do routine activities for more than half of their normal waking hours.
- This study is for people age 18 and older.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Participants with FGFR3-mutant or -fusion noninvasive bladder tumors
25 participants with FGFR3-mutant or -fusion noninvasive bladder tumors will be accrued.
|
Participants will receive erdafitinib at a dose of 6 mg orally once daily for the first 14 days (±3 days).
Serum phosphate levels will be assessed on day 14 (±3 days) and the dose of erdafitinib may be lowered based on the serum phosphate level.
Treatment with erdafitinib at a dose of 6 mg orally once daily, or at a lower dose level for another 14 days (±3 days) until the day of their standard-of-care TURBT/biopsy.
Standard-of-care TURBT/biopsy will be performed after approximately 28 days (±5 days) from the start of treatment with erdafitinib, and biologic and pathologic tumor response will be assessed.
All participants will then be followed up for recurrence or progression in accordance with the standard of care.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate
Time Frame: 3 weeks after first study treatment
|
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).
|
3 weeks after first study treatment
|
Collaborators and Investigators
Investigators
- Principal Investigator: Eugene Pietzak, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Urinary Bladder Diseases
- Disease Attributes
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Recurrence
- Urinary Bladder Neoplasms
Other Study ID Numbers
- 21-166
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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