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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03773302
Registration number
NCT03773302
Ethics application status
Date submitted
10/12/2018
Date registered
12/12/2018
Titles & IDs
Public title
Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
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Scientific title
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
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Secondary ID [1]
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2018-004004-19
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Secondary ID [2]
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QBGJ398-301
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Advanced Cholangiocarcinoma
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FGFR2 Gene Mutation
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Condition category
Condition code
Cancer
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Biliary tree (gall bladder and bile duct)
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Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - BGJ398
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin
Experimental: Infigratinib (BGJ398) 125 mg - Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
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.
Treatment: Drugs: BGJ398
Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
Treatment: Drugs: 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.
Treatment: Drugs: 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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Progression-free Survival (Central Imaging Assessment)
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Assessment method [1]
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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.
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Timepoint [1]
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From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment.
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Secondary outcome [1]
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Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin
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Assessment method [1]
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OS by investigator assessment, defined as time from date of randomization until death due to any cause
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Timepoint [1]
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From the time of randomization to time of death. Note: OS is an event driven endpoint. Subjects who had not died (no record of death) or were lost to follow-up were censored at the date of last known to be alive.
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Secondary outcome [2]
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Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin
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Assessment method [2]
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Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
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Timepoint [2]
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From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment.
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Secondary outcome [3]
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Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment
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Assessment method [3]
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ORR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR) or confirmed complete response (CR) as assessed by BICR and the investigator according to RECIST v1.1 among patients with measurable disease at baseline
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Timepoint [3]
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From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
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Secondary outcome [4]
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Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator.
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Assessment method [4]
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BOR was defined as the best response a subject ever achieved after study treatment prior to crossover and any subsequent anticancer therapy, complete response (CR) and partial response (PR) were claimed only if the criteria for each were met at a subsequent time point at least 4 weeks apart. In the case of stable disease (SD), measurements must have met the SD criteria at least once post-baseline no less than 6 weeks from the randomization date.
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Timepoint [4]
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From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
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Secondary outcome [5]
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Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator.
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Assessment method [5]
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DOR is defined as the time from initiation of confirmed partial response (PR) or confirmed complete response (CR) to the time of confirmed progressive disease (PD) or death. If subjects do not reach PD or death before crossover, the DOR is censored at the last valid tumor assessment before crossover.
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Timepoint [5]
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From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
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Secondary outcome [6]
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Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator.
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Assessment method [6]
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DCR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR), confirmed complete response (CR) or stable disease (SD) or non-CR/non-PD before crossover.
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Timepoint [6]
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From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
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Secondary outcome [7]
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Number of Participants With Adverse Events (AEs)
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Assessment method [7]
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Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period
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Timepoint [7]
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From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm).
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Secondary outcome [8]
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Number of Participants With Serious Adverse Events (SAEs)
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Assessment method [8]
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Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period
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Timepoint [8]
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From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm).
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Eligibility
Key inclusion criteria
* Histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma are not eligible
* Have written documentation of local laboratory or central laboratory determination of a known or likely activating FGFR2 fusion/rearrangement from a sample collected before randomization
* Have an archival tumor tissue sample available with sufficient tumor content for FGFR2 fusion/rearrangement molecular testing by the central laboratory. However, if an archival tumor tissue sample is not available, or does not meet requirements for central testing a newly obtained (before randomization) tumor biopsy may be submitted instead. If a prestudy written documentation of FGFR2 fusion/rearrangement in tumor tissue is available from the central laboratory, an additional tumor sample does not need to be submitted.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Are able to swallow and retain oral medication
* Are willingness to avoid pregnancy or father children
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma, with following exceptions
1. Prior neoadjuvant or adjuvant therapy is permitted if completed > 6 months after the last dose of neoadjuvant or adjuvant therapy.
2. One cycle of gemcitabine-based chemotherapy for locally advanced or metastatic cholangiocarcinoma is permitted before randomization
* 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 moderate or 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
* Have any contraindication to cisplatin or gemcitabine treatment according to local labeling or standard institutional practice.
* Have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.
* Have received a live vaccine within 30 days before the first dose of study drug or are planning to receive a live vaccine during participation in this study
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
27/12/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
2/03/2023
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Sample size
Target
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Accrual to date
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Final
48
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Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
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Recruitment hospital [1]
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Chris O'Brien Lifehouse Hospital - Camperdown
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Blacktown Hospital - Darlinghurst
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Royal Adelaide Hospital - Adelaide
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Monash Medical Centre - Bentleigh East
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Peninsula & South Eastern Haematology and Oncology Group - Frankston
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St John of God Hospital Subiaco - Subiaco
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Recruitment postcode(s) [1]
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- Camperdown
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- Darlinghurst
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- Adelaide
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Recruitment postcode(s) [4]
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- Bentleigh East
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- Frankston
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Recruitment postcode(s) [6]
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- Subiaco
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Recruitment outside Australia
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Chiang Mai
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Phitsanulok
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London
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
QED Therapeutics, Inc.
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Helsinn Healthcare SA
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Ethics approval
Ethics application status
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Summary
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 fusion/rearrangement. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.
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Trial website
https://clinicaltrials.gov/study/NCT03773302
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Trial related presentations / 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 Oct;16(30):2375-2384. doi: 10.2217/fon-2020-0299. Epub 2020 Jun 25.
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Public notes
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Contacts
Principal investigator
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Clinical Development
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QED Therapeutics
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/02/NCT03773302/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/02/NCT03773302/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03773302