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Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations

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ClinicalTrials.gov Identifier: NCT03773302
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : July 30, 2020
Sponsor:
Information provided by (Responsible Party):
QED Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE December 10, 2018
First Posted Date  ICMJE December 12, 2018
Last Update Posted Date July 30, 2020
Actual Study Start Date  ICMJE December 27, 2019
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2020)
Progression-free survival (central imaging assessment) [ Time Frame: Approximately 11 months on average ]
Defined as the time from randomization until date of disease progression by blinded independent central imaging assessment (Response Evaluation Criteria in Solid Tumors [RECIST] v. 1.1) or death, whichever occurs first.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
Number of participants with progression-free survival (Central Imaging Assessment) [ Time Frame: Month 12 ]
Defined as the time from randomization until date of disease progression by central independent imaging assessment (Response Evaluation Criteria in Solid Tumors [RECIST] v. 1.1) or death, whichever occurs first.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2020)
  • Overall survival in participants treated with infigratinib versus gemcitabine with cisplatin [ Time Frame: Approximately 15 months on average ]
    Defined as time from date of randomization until death due to any cause
  • Investigator assessed progression free survival in participants treated with infigratinib compared to gemcitabine and cisplatin [ Time Frame: Approximately 10 months on average ]
    Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
  • Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by overall response rate (ORR) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
  • Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by best overall response (BOR) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
  • Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by duration of response (DOR) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
  • Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by disease control rate (PR+CR+SD) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
  • Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability of infigratinib. [ Time Frame: Approximately from baseline to last dose date of study treatment + 30 days, approximately 12 months on average ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • Percentage of overall survival in participants treated with infigratinib versus gemcitabine with cisplatin [ Time Frame: Month 12 ]
    Defined as time from date of randomization until death due to any cause
  • Percentage of investigator assessed progression free survival in participants treated with infigratinib compared to gemcitabine and cisplatin [ Time Frame: Month 12 ]
    Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
Official Title  ICMJE A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib Versus Gemcitabine With Cisplatin in Subjects With Advanced/Metastatic or Inoperable Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations: The PROOF Trial
Brief Summary Infigratinib is an oral drug which selectively binds to fibroblast growth factor receptor (FGFR) 2 and is being developed to treat participants with FGFR2 mutated cholangiocarcinoma. The purpose of the study is to evaluate the efficacy and safety of the investigational agent oral infigratinib vs standard of care chemotherapy (gemcitabine plus cisplatin) in first-line treatment of participants with unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions/translocations. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Cholangiocarcinoma
  • FGFR2 Gene Mutation
Intervention  ICMJE
  • Drug: BGJ398
    Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
    Other Name: Infigratinib
  • Drug: Gemcitabine
    Gemcitabine 1000 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.
  • Drug: Cisplatin
    Cisplatin 25 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.
Study Arms  ICMJE
  • Experimental: Infigratinib (BGJ398) 125 mg
    Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
    Intervention: Drug: BGJ398
  • Active Comparator: Gemcitabine + Cisplatin
    Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met.
    Interventions:
    • Drug: Gemcitabine
    • Drug: Cisplatin
Publications * Makawita S, K Abou-Alfa G, Roychowdhury S, Sadeghi S, Borbath I, Goyal L, Cohn A, Lamarca A, Oh DY, Macarulla T, T Shroff R, Howland M, Li A, Cho T, Pande A, Javle M. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020 Jun 25. doi: 10.2217/fon-2020-0299. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 17, 2020)
384
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2018)
350
Estimated Study Completion Date  ICMJE September 30, 2024
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma are not eligible
  • Documented FGFR2 gene fusions/translocations
  • Have an archival tissue sample available with sufficient tumor for central FGFR2 fusion/translocation molecular testing. However, if an archival tissue sample is not available, a newly obtained (before randomization) tumor biopsy may be submitted instead.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Able to swallow and retain oral medication
  • Willingness to avoid pregnancy or father children

Exclusion Criteria:

  • Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma. Prior neoadjuvant or adjuvant therapy is permitted if completed > 6 months after the last dose of neoadjuvant or adjuvant therapy.
  • History of a liver transplant
  • Received previously or currently is receiving treatment with a mitogen activated protein kinase kinase (MEK) or selective FGFR inhibitor
  • Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (such as, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
  • Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
  • History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
  • Current evidence of corneal or retinal disorder/keratopathy
  • Receiving and continued treatment or are planning to receive agents or consuming foods that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration
  • Clinically significant or uncontrolled cardiac disease
  • Recent (≤ 3 months prior to first dose of study drug) transient ischemic attack or stroke
  • Severe hearing loss
  • Severe neuropathy
  • History of another primary malignancy within 3 years except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer or other curatively treated malignancy that is not expected to require treatment
  • Pregnant or breastfeeding
  • Have known microsatellite instability-high (MSI-H) disease and the decision is made by the treating investigator that an alternative, non-study therapy is warranted according to standard of care.
  • Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents, infigratinib, or their excipients
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: QED Therapeutics Clinical Development 877-280-5655 PROOF301.ct@qedtx.com
Contact: QED Therapeutics Chief Medical Officer PROOF301.ct@qedtx.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Italy,   Korea, Republic of,   Puerto Rico,   Spain,   Taiwan,   Thailand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03773302
Other Study ID Numbers  ICMJE QBGJ398-301
2018-004004-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party QED Therapeutics, Inc.
Study Sponsor  ICMJE QED Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Development QED Therapeutics
PRS Account QED Therapeutics, Inc.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP