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

Primary Purpose

Bladder Cancer, Recurrent Bladder Cancer, FGFR3 Gene Mutation

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Erdafitinib
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring Non-Muscle Invasive Bladder Cancer, NMIBC, Erdafitinib, FGFR3, 21-166, Memorial Sloan Kettering Cancer Center

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Commack (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Participants with FGFR3-mutant or -fusion noninvasive bladder tumors

Arm Description

25 participants with FGFR3-mutant or -fusion noninvasive bladder tumors will be accrued.

Outcomes

Primary Outcome Measures

Objective response rate
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).

Secondary Outcome Measures

Full Information

First Posted
June 2, 2021
Last Updated
October 13, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04917809
Brief Title
A Study of Oral 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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 17, 2022 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to assess the effectiveness of erdafitinib in people with non-muscle invasive bladder cancer (NMIBC) that has come back after standard treatment, such as Bacillus Calmette-Guerin (BCG) or chemotherapy instilled into the bladder. Participants in this study will have bladder cancer with a mutation in the FGFR3 gene. FGFR3 mutations are the most common genetic alteration in NMIBC and is present in the majority of recurrent NMIBC tumors. Genetic testing of the participant's prior or recurrent NMIBC tumor will be performed to confirm it has an FGFR3 gene mutation. Erdafitinib is a pill given orally (by mouth) that blocks the protein made by this altered gene, which may stop cancer cells from growing. Erdafitinib is already used as an approved treatment for metastatic bladder cancer. Researchers are doing this study to determine whether erdafitinib is an effective treatment for FGFR3-altered non-muscle invasive bladder cancer in the time period between when a recurrent tumor is identified and a TURBT (transurethral resection of a bladder tumor) or biopsy procedure is performed to remove it.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Recurrent Bladder Cancer, FGFR3 Gene Mutation
Keywords
Non-Muscle Invasive Bladder Cancer, NMIBC, Erdafitinib, FGFR3, 21-166, Memorial Sloan Kettering Cancer Center

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Participants with FGFR3-mutant or -fusion noninvasive bladder tumors
Arm Type
Experimental
Arm Description
25 participants with FGFR3-mutant or -fusion noninvasive bladder tumors will be accrued.
Intervention Type
Drug
Intervention Name(s)
Erdafitinib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective response rate
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).
Time Frame
3 weeks after first study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Email
pietzake@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Gopakumar Iyer, MD
Phone
646-888-4737
Email
iyerg@mskcc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Commack (Limited Protocol Activities)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, PhD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

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

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