Clinical Trials /

Study of Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations

NCT04197986

Description:

This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy of giving an oral targeted FGFR1-3 inhibitor, infigratinib, as adjuvant treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations (mutations, and gene fusions or translocations [ie, rearrangements) who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy or upper tract urothelial cancer post distal ureterectomy and/or nephrectomy. Study treatment is randomized between infigratinib or placebo with treatment until invasive local or distal disease recurrence.

Related Conditions:
  • Bladder Urothelial Carcinoma
  • Renal Pelvis and Ureter Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations
  • Official Title: Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)

Clinical Trial IDs

  • ORG STUDY ID: QBGJ398-302
  • SECONDARY ID: 2019-003248-63
  • NCT ID: NCT04197986

Conditions

  • Upper Tract Urothelial Carcinomas
  • Urothelial Bladder Cancer

Interventions

DrugSynonymsArms
InfigratinibIP, Study drugInfigratinib 125 mg
PlaceboPlacebo

Purpose

This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy of giving an oral targeted FGFR1-3 inhibitor, infigratinib, as adjuvant treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations (mutations, and gene fusions or translocations [ie, rearrangements) who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy or upper tract urothelial cancer post distal ureterectomy and/or nephrectomy. Study treatment is randomized between infigratinib or placebo with treatment until invasive local or distal disease recurrence.

Trial Arms

NameTypeDescriptionInterventions
Infigratinib 125 mgExperimentalParticipants will be randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks
  • Infigratinib
PlaceboPlacebo ComparatorParticipants will be randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks
  • Placebo

Eligibility Criteria

        Inclusion Criteria

          1. Have histologically or cytologically confirmed, invasive urothelial carcinoma with
             susceptible FGFR3 alterations within 120 days following nephroureterectomy, distal
             ureterectomy, or cystectomy

          2. If the patient received neoadjuvant chemotherapy, pathologic stage at surgical
             resection must be AJCC Stage ≥ ypT2 and/or yN+.

          3. If the patient did not receive neoadjuvant chemotherapy:

               1. Must be ineligible to receive cisplatin-based adjuvant chemotherapy per the
                  Galsky criteria:

                    -  creatinine clearance < 60cc/min or

                    -  ≥ Grade 2 hearing loss or

                    -  ≥ Grade 2 neuropathy)

               2. Pathologic stage must be AJCC Stage ≥pT2 pN0-2 M0 (post-lymphadenectomy or no
                  lymphadenectomy [pNx]) for upper tract disease.

               3. Pathologic stage should be AJCC Stage ≥pT3 or pN+ (bladder cancer).

          4. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

          5. Patients must have no evidence of metastatic disease based on screening CT or MRI.

        Exclusion Criteria:

          1. Presence of positive surgical margins following nephroureterectomy, distal
             ureterectomy, or cystectomy.

          2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for
             Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.

          3. Have previously or currently is receiving treatment with a mitogen-activated protein
             kinase (MEK) or selective FGFR inhibitor.

          4. Have impaired gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of oral infigratinib (eg, active ulcerative diseases,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel
             resection)

          5. Have current evidence of corneal or retinal disorder/keratopathy.

          6. Have a history and/or current evidence of extensive tissue calcification.

          7. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg,
             parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis),
             unless well controlled.

          8. Are currently receiving or are planning to receive during participation in this study,
             treatment with agents that are known strong inducers or inhibitors of CYP3A4 and
             medications which increase serum phosphorus and/or calcium concentration.

          9. Clinically significant cardiac disease.

         10. Recent (< 3 months prior to first dose of study drug) transient ischemic attack or
             stroke.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Centrally determine disease-free survival (DFS)
Time Frame:Randomization through 1 year after end of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Compare DFS including intraluminal low-risk recurrence
Time Frame:Randomization through up to an approximated 5 years (60 months) after end of treatment
Safety Issue:
Description:
Measure:Compare metastasis-free survival (MFS)
Time Frame:Randomization through 1 year after end of treatment
Safety Issue:
Description:
Measure:Compare overall survival (OS)
Time Frame:Randomization through 1 year after end of treatment
Safety Issue:
Description:
Measure:Compare investigator-reviewed DFS
Time Frame:Randomization through 1 year after end of treatment
Safety Issue:
Description:
Measure:Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability
Time Frame:30-Day Post-Treatment
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:QED Therapeutics, Inc.

Trial Keywords

  • FGFR3 Genetic Alterations
  • upper tract urothelial carcinomas
  • UTUC
  • Invasive Urothelial Carcinoma
  • Fibroblast growth factor receptor inhibitor
  • BGJ398
  • FGFR3
  • urothelial bladder cancer
  • UBC
  • Infigratinib phosphate
  • Infigratinib
  • Adjuvant

Last Updated

December 30, 2019