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

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ClinicalTrials.gov Identifier: NCT04197986
Recruitment Status : Recruiting
First Posted : December 13, 2019
Last Update Posted : December 24, 2020
Sponsor:
Information provided by (Responsible Party):
QED Therapeutics, Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Upper Tract Urothelial Carcinomas Urothelial Bladder Cancer Drug: Infigratinib Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 218 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomly assigned (1:1) to receive oral infigratinib phosphate or placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: As a double-blind study, participants, investigators, study monitor(s) and the clinical study team will be blinded to the treatment administered.
Primary Purpose: Treatment
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)
Actual Study Start Date : March 11, 2020
Estimated Primary Completion Date : January 31, 2024
Estimated Study Completion Date : January 31, 2025

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Infigratinib 125 mg
Participants 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
 Drug: Infigratinib
Participants randomly assigned to infigratinib will receive hard gelatin capsules for oral administration of infigratinib 125 mg once a day (administered as one 100-mg capsule and one 25-mg capsule) using a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.
Other Names:
  • IP
  • Study drug
Placebo Comparator: Placebo
Participants 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
 Drug: Placebo
Participants randomly assigned to placebo will receive placebo matching in appearance the investigational product (infigratinib), which will be provided as hard gelatin capsules for oral use and will be administered once daily on a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.


Outcome Measures
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Primary Outcome Measures :
  1. Centrally determine disease-free survival (DFS) [ Time Frame: Randomization through 1 year after end of treatment ]

Secondary Outcome Measures :
  1. Compare DFS including intraluminal low-risk recurrence [ Time Frame: Randomization through up to an approximated 5 years (60 months) after end of treatment ]
  2. Compare metastasis-free survival (MFS) [ Time Frame: Randomization through 1 year after end of treatment ]
  3. Compare overall survival (OS) [ Time Frame: Randomization through 1 year after end of treatment ]
  4. Compare investigator-reviewed DFS [ Time Frame: Randomization through 1 year after end of treatment ]
  5. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04197986


Contacts
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Contact: QED Therapeutics 1-877-280-5655 Proof302.ct@qedtx.com

Locations
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Sponsors and Collaborators
QED Therapeutics, Inc.
Investigators
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Study Director: Corina Andresen, MD QED Therapeutics
More Information
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Responsible Party: QED Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04197986    
Other Study ID Numbers: QBGJ398-302
2019-003248-63 ( EudraCT Number )
First Posted: December 13, 2019    Key Record Dates
Last Update Posted: December 24, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by QED Therapeutics, Inc.:
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
Additional relevant MeSH terms:
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Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
 Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases