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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04197986
Recruitment Status : Recruiting
First Posted : December 13, 2019
Last Update Posted : October 8, 2020
Information provided by (Responsible Party):
QED Therapeutics, Inc.

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

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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

Resource links provided by the National Library of Medicine

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.

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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT04197986

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Contact: QED Therapeutics 1-877-280-5655

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United States, Arizona
Arizona Oncology Associates Recruiting
Tucson, Arizona, United States, 85711
Contact: Stacey Kimbell    520-668-5678   
Principal Investigator: Christopher Disimone, MD         
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Sumanta Pal, M.D.    626-256-4673      
Principal Investigator: Sumanta Pal, M.D.         
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Cheryl Kefauver    323-865-3000   
Principal Investigator: Siamak Daneshmand, MD         
United States, Florida
Urological Research Network CORP Recruiting
Hialeah, Florida, United States, 33016
Contact: Isabel H Lopez    786-431-2014   
Principal Investigator: Fernando J Bianco, MD         
Woodlands Medical Specialist Recruiting
Pensacola, Florida, United States, 32503
Contact: Leslie Bellamy    850-696-4423   
Principal Investigator: Rami Owera, MD         
United States, Ohio
Oncology Hematology Care Recruiting
Cincinnati, Ohio, United States, 45242
Contact: Doug Hart    513-751-2273   
Principal Investigator: David Waterhouse, MD         
United States, Tennessee
Urology Associates, P.C. Recruiting
Nashville, Tennessee, United States, 37209
Contact: Roxie Felton    615-250-9240   
Principal Investigator: Gautam Jayram, M.D.         
United States, Texas
Houston Methodist Hospital- Department of Urology Recruiting
Houston, Texas, United States, 77030
Contact: Cinthya Yesenia Obando Perez Obando Perez, MD    346-238-6123   
Principal Investigator: Raj Satkunasivam, MD         
Texas Oncology Recruiting
Longview, Texas, United States, 75601
Contact: Shelly Maxfield    903-757-2122   
Principal Investigator: John Lijo, MD         
Canada, British Columbia
BC Cancer- Vancouver Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Lyn Lorenzen    604.877.6000   
Principal Investigator: Bernard J. Eigl, MD         
Canada, Quebec
McGill University Health Centre (MUHC) Recruiting
Montréal, Quebec, Canada, H4A 3J1
Contact: Dianna Leroux    514-934-1934 ext 35161   
Principal Investigator: Wassim Kassouf, MD         
Caritas - Krankenhaus St. Josef Recruiting
Regensburg, Bayern, Germany, 93053
Contact: Kathrin Hese    +49 941 782 3510   
Principal Investigator: Marco Schnabel         
Urologicum Duisburg Recruiting
Duisburg, Nordrhein-WestFalen, Germany, 47179
Contact: Claudia Kleinfeld    +49 203 500304-0   
Principal Investigator: Eva Hellmis         
Marien Hospital Herne - Universitätsklinikum der Ruhr-Universität Bochum Recruiting
Herne, Nordrhein-Westfalen, Germany, 44625
Contact: Ayleen Bartels    +49 2323 499 5252   
Principal Investigator: Florian Roghmann         
United Kingdom
Sarah Cannon Research Institute London Recruiting
London, England, United Kingdom, W1G 6AD
Contact: Tasmia Manir    0203.219.5200   
Principal Investigator: Anna Patrikidou, MD, PhD         
Sponsors and Collaborators
QED Therapeutics, Inc.
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Study Director: Corina Andresen, MD QED Therapeutics
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Responsible Party: QED Therapeutics, Inc. Identifier: NCT04197986    
Other Study ID Numbers: QBGJ398-302
2019-003248-63 ( EudraCT Number )
First Posted: December 13, 2019    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: March 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
Invasive Urothelial Carcinoma
Fibroblast growth factor receptor inhibitor
urothelial bladder cancer
Infigratinib phosphate
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases