Rogaratinib for BCG Refractory High Risk Non-Muscle Invasive Bladder Cancer With FGFR1/2 Overexpression

NCT04040725 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 19-205
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This research study is studying the safety, tolerability, and tumor activity of the study drug known as rogaratinib as a possible treatment for bladder cancer.

Conditions

Bladder Cancer

Keywords

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Complete Response

  Absence of any cancer in the bladder (No carcinoma in situ or new lesions) on examination with TURBT

  6 months

Secondary Outcomes (2)

• Duration of Response

  2 years

• Rate Toxicity Occurs

  2 years

Study Arms (1)

Rogaratinib

EXPERIMENTAL

* Rogaratinib is administered orally twice daily * Rogaratinib is held for 72 hours before cystoscopy/TURBT and if no complications are seen, treatment is resumed 24 hours after the TURBT

Drug: Rogaratinib

Interventions

Rogaratinib DRUG

Rogaratinib is an oral drug that inhibits FGFR. Mutations in FGFR help bladder cancer grow.

Rogaratinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age (at least age of legal maturity)
• Have a histologically-confirmed diagnosis of high risk non-muscle-invasive (T1, High Grade Ta and/or CIS) transitional cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are not allowed.
• In subjects with Ta and T1, have undergone complete TURBT as characterized by:
• Attainment of a visually complete resection
• Residual CIS not amenable to complete transurethral resection is acceptable
• The most recent cystoscopy / TURBT must have been performed within 8 weeks prior to the first dose of trial treatment
• Have been treated with adequate BCG therapy and have developed NMIBC that is unresponsive to BCG therapy. Adequate BCG therapy must include: An induction course with at least 5 instillations of BCG (adequate induction); and at least 7 instillations of BCG within 9 months of the first instillation of adequate induction therapy. BCG unresponsive high risk NMIBC is defined as: Stage progression at 3 months (±4 weeks) despite adequate induction therapy (e.g., Ta to T1, or CIS to T1; note: adequate induction therapy only, defined above, is required in this case); or Persistent high risk NMIBC at 6 months (±4 weeks) after adequate BCG therapy or Recurrent high risk NMIBC within 9 months of the last BCG instillation despite adequate BCG therapy.
• Have elected not to undergo, or are considered ineligible for radical cystectomy, as determined by the treating surgeon. Reasons for ineligibility or refusal of radical cystectomy should be discussed with the subject as part of the informed consent process and should be captured on the appropriate case report form. Ineligibility factors for radical cystectomy may include, but are not limited to:
• Cardiovascular disease (e.g. recent acute coronary syndrome, arrhythmia, heart failure)
• Chronic obstructive pulmonary disease that would preclude a safe surgical procedure, as determined by the treating surgeon
• Poor performance status (e.g. ECOG \>2)
• Prior major abdominal and pelvic surgery, that would preclude a safe surgical procedure, as determined by the treating surgeon
• High FGFR 1/3 mRNA expression levels (RNAscope score of 3+ or 4+; measurement is part of the protocol) in archival or fresh tumor biopsy specimen
• Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression testing. Patients who don't have archival tissue specimens meeting eligibility requirements may undergo a biopsy. Acceptable samples include core needle biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
• Ability to understand and signing of the written patient information/informed consent form (PI/ICF) for FGFR testing

You may not qualify if:

• Has muscle invasive (i.e. T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma.
• Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has undergone any intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting trial treatment. (Note: intravesical treatment given as part of the most recent cystoscopy / TURBT is allowed.)
• Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies).
• Previous or concurrent cancer except: cervical carcinoma in situ, treated basal-cell carcinoma or squamous cell skin cancer, localized prostate cancer treated with curative intent and known absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL undergoing active surveillance and treatment-naïve), or any other cancer curatively treated \> 3 years before the first study drug administration.
• History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
• Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms of angina at rest)
• New-onset angina (within last 3 months before the first study drug administration)
• Myocardial infarction (MI) within past 6 months before the first study drug administration
• Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with arrhythmia not requiring therapy or under control with anti-arrhythmic therapy such as beta-blockers or digoxin are eligible.
• Patients with known coronary artery disease, or congestive heart failure not meeting the above criteria, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
• Known human immunodeficiency virus (HIV) infection.
• Active hepatitis B virus (HBV; chronic or acute; defined as having a known positive hepatitis B surface antigen \[HBsAg\] test at the time of screening) or hepatitis C infection requiring treatment. Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of HBsAg) are eligible if HBV DNA is negative. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bayer: collaborator

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Rogaratinib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Bradley A. McGregor, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 1, 2019
• Study Start: November 27, 2019
• Primary Completion: November 27, 2019
• Study Completion: November 27, 2019
• Last Updated: December 17, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu