Phase I BLASST-3 Trial

NCT04972253 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 21-162
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this research is to see whether using a drug that blocks a protein called FGFR (fibroblast growth factor receptor) prior to surgery is safe and effective in patients with bladder cancer that have mutations in FGFR3 or FGFR2 and who cannot receive chemotherapy with cisplatin prior to surgery The name of the study drug involved in this study is: \- Infigratinib

Conditions

Bladder Transitional Cell Carcinoma; Bladder Cancer; Fibroblast Growth Factor Receptor

Keywords

Bladder transitional cell carcinoma; Bladder Cancer; Fibroblast growth factor receptor

Outcome Measures

Primary Outcomes (1)

• ≥ 70% of patients receiving at least 1 dose of study treatment followed by completion of radical cystectomy (Feasibility)

  Feasibility is defined as ≥ 70% of patients receiving at least 1 dose of study treatment followed by completion of radical cystectomy in the absence of DLT up to 4 weeks post-RC. Dose-limiting toxicities (DLTs) will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria). DLT will be defined as an adverse event (AE) or abnormal laboratory value deemed related to therapy with infigratinib, including those AEs and abnormal laboratory values that result in a failure to meet the criteria for re-treatment.

  time of first administration of study treatment until 4 weeks after RC up to 3 months

Secondary Outcomes (4)

• Pathologic response (<ypT2N0) at time of RC.

  3 months

• Pathologic complete response (pCR) at time of RC.

  3 months

• Relapse-free survival (RFS) after RC.

  4 weeks after end of treatment, then every 12-24 weeks up to 1 year

• Progression-free proportion after neoadjuvant infigratinib, prior to RC

  2 months

Study Arms (1)

Infigratinib

EXPERIMENTAL

* Infigratinib daily dosage per protocol 3-week on/1-week off schedule. 4 weeks will constitute 1 cycle of therapy. * Participants will receive 2 cycles (i.e. 8 weeks) and the treatment will be administered as an outpatient. * After completion of therapy, patients will undergo a CT of the chest, abdomen and pelvis (within 2 weeks of the last dose of therapy) and then proceed to Radical cystectomy 2-4 weeks after the last dose of therapy.

Drug: Infigratinib

Interventions

Infigratinib DRUG

Oral, dosage per protocol

Also known as: BGJ-398

Infigratinib

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization (e.g. HIPAA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years at time of study entry (no safety data in pediatric patients is available for infigratinib).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A).
• Histologically confirmed bladder transitional cell carcinoma (TCC)
• \-- Patients with mixed histology are required to have a component of TCC, and no component of small cell histology
• cT2-T4a N0 M0 disease after radiographic staging of chest, abdomen and pelvis, considered appropriate and planned for radical cystectomy as assessed by a Urologic Oncologist.
• Presence of the following FGFR3/2 activating alterations, as detected by either plasma or urine cfDNA or cfRNA or by tissue-based NGS (Predicine, Hayward, CA):
• Mutations in exon 7 (R248C, S249C)
• Mutations in exon 10 (G372C, A393E, Y375C)
• Mutations in exon 15 (K652M/T, K652E/Q)
• Any FGFR3/2 gene fusion (Availability of baseline archival tumor tissue for identification of FGFR3/2 alterations is not required, but tissue will be obtained when available including either FFPE tumor tissue block or a minimum of fifteen 5μm unstained FFPE slides and fifteen 10μm unstained FFPE slides with an associated pathology report is required)
• Ineligibility for cisplatin-based chemotherapy, defined by any of the following:
• Creatinine clearance (CL) \<60 mL/min. GFR should be calculated from serum/plasma creatinine using the Cockcroft-Gault formula.
• CTCAE v5.0 Grade \> 1 hearing loss
• CTCAE v5.0 Grade \> 1 neuropathy

You may not qualify if:

• Patients with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder
• Inoperable tumor(s) with fixation to the pelvic wall on clinical exam
• Any previous systemic chemotherapy or radiotherapy for TCC of bladder
• Participation in another clinical study with an investigational product during the last 6 months
• Any prior participation in a study involving an FGFR inhibitor.
• Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease (e.g. cervical cancer in situ)
• Receipt of the last dose of intravesical chemotherapy or biologic therapy ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have received prior intravesical chemotherapy or biologic therapy (e.g. BCG)
• Patients currently receiving treatment with drugs that are known to be strong CYP3A4 inducers or inhibitors, including anti-epileptic drugs.
• Use of medications that are known to prolong the QT interval and/or associated with a risk of torsade de pointes 7 days prior to the first dose of infigratinib.
• Use of amiodarone within 90 days prior to first dose of infigratinib.
• Use of medications that increase serum levels of calcium and/or phosphorus.

Sponsors & Collaborators

• Guru P. Sonpavde: lead
• QED Therapeutics, a BridgeBio company: collaborator

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Acrocephalosyndactylia

Interventions

infigratinib

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; Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Guru Sonpavde, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: July 22, 2021
• Study Start: December 23, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: August 10, 2022

Record last verified: 2022-08

Data Sharing

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