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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03773302




Registration number
NCT03773302
Ethics application status
Date submitted
10/12/2018
Date registered
12/12/2018
Date last updated
30/07/2020

Titles & IDs
Public title
Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
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
Secondary ID [1] 0 0
2018-004004-19
Secondary ID [2] 0 0
QBGJ398-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cholangiocarcinoma 0 0
FGFR2 Gene Mutation 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (central imaging assessment) - 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.
Timepoint [1] 0 0
Approximately 11 months on average
Secondary outcome [1] 0 0
Overall survival in participants treated with infigratinib versus gemcitabine with cisplatin - Defined as time from date of randomization until death due to any cause
Timepoint [1] 0 0
Approximately 15 months on average
Secondary outcome [2] 0 0
Investigator assessed progression free survival in participants treated with infigratinib compared to gemcitabine and cisplatin - Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
Timepoint [2] 0 0
Approximately 10 months on average
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Approximately 10 months on average
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Approximately 10 months on average
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Approximately 10 months on average
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Approximately 10 months on average
Secondary outcome [7] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability of infigratinib.
Timepoint [7] 0 0
Approximately from baseline to last dose date of study treatment + 30 days, approximately 12 months on average

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

- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse Hospital - Camperdown
Recruitment hospital [2] 0 0
Blacktown Hospital - Darlinghurst
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Monash Medical Centre - Bentleigh East
Recruitment hospital [5] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [6] 0 0
St John of God Hospital Subiaco - Subiaco
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
- Bentleigh East
Recruitment postcode(s) [5] 0 0
- Frankston
Recruitment postcode(s) [6] 0 0
- Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
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United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
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Louisiana
Country [9] 0 0
United States of America
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Maryland
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United States of America
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Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
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New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
Belgium
State/province [20] 0 0
Brussels
Country [21] 0 0
Belgium
State/province [21] 0 0
Charleroi
Country [22] 0 0
Belgium
State/province [22] 0 0
Edegem
Country [23] 0 0
Canada
State/province [23] 0 0
Alberta
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
France
State/province [26] 0 0
Dijon
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France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Nice
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
Italy
State/province [30] 0 0
Cremona
Country [31] 0 0
Italy
State/province [31] 0 0
Meldola
Country [32] 0 0
Italy
State/province [32] 0 0
Milano
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Pusan
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seongnam-si
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Suwon-si
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Puerto Rico
State/province [37] 0 0
Rio Piedras
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Spain
State/province [38] 0 0
Andalucia
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Spain
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Aragon
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Spain
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Castilla Y Leon
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Spain
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Cataluna
Country [42] 0 0
Spain
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Barcelona
Country [43] 0 0
Spain
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Madrid
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Taiwan
State/province [44] 0 0
Tainan
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Taiwan
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Kaohsiung
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Taiwan
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Taichung City
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Taiwan
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Taipei
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Taiwan
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Taoyuan City
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Thailand
State/province [49] 0 0
Songkla
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Thailand
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Bangkok
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Thailand
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Chiang Mai
Country [52] 0 0
Thailand
State/province [52] 0 0
Khon Kaen
Country [53] 0 0
Thailand
State/province [53] 0 0
Phitsanulok

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
QED Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

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 gene fusions/translocations. Subjects will be randomized 2:1 to receive
infigratinib or gemcitabine plus cisplatin.
Trial website
https://clinicaltrials.gov/show/NCT03773302
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Development
Address 0 0
QED Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
QED Therapeutics Clinical Development
Address 0 0
Country 0 0
Phone 0 0
877-280-5655
Fax 0 0
Email 0 0
PROOF301.ct@qedtx.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03773302