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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
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)
Timepoint [1] 0 0
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.
Secondary outcome [1] 0 0
Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment
Timepoint [3] 0 0
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).
Secondary outcome [4] 0 0
Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator.
Timepoint [4] 0 0
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).
Secondary outcome [5] 0 0
Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator.
Timepoint [5] 0 0
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).
Secondary outcome [6] 0 0
Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator.
Timepoint [6] 0 0
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).
Secondary outcome [7] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [7] 0 0
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).
Secondary outcome [8] 0 0
Number of Participants With Serious Adverse Events (SAEs)
Timepoint [8] 0 0
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).

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
Minimum age
18 Years
Maximum age
No limit
Sex
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, 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

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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/03/2023
Sample size
Target
Accrual to date
Final
48
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
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Belgium
State/province [15] 0 0
Brussels
Country [16] 0 0
Belgium
State/province [16] 0 0
Charleroi
Country [17] 0 0
Belgium
State/province [17] 0 0
Edegem
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Changsha
Country [23] 0 0
China
State/province [23] 0 0
Guangzhou
Country [24] 0 0
China
State/province [24] 0 0
Hubei
Country [25] 0 0
China
State/province [25] 0 0
Shenyang
Country [26] 0 0
China
State/province [26] 0 0
Zhongshan
Country [27] 0 0
France
State/province [27] 0 0
Val-de-Marne
Country [28] 0 0
France
State/province [28] 0 0
Dijon
Country [29] 0 0
France
State/province [29] 0 0
Lille
Country [30] 0 0
France
State/province [30] 0 0
Lyon
Country [31] 0 0
France
State/province [31] 0 0
Montbéliard
Country [32] 0 0
France
State/province [32] 0 0
Nice
Country [33] 0 0
France
State/province [33] 0 0
Paris
Country [34] 0 0
Germany
State/province [34] 0 0
Baden-Wurttemberg
Country [35] 0 0
Germany
State/province [35] 0 0
Bayern
Country [36] 0 0
Germany
State/province [36] 0 0
Dortmund
Country [37] 0 0
Germany
State/province [37] 0 0
Heidelberg
Country [38] 0 0
Italy
State/province [38] 0 0
Cremona
Country [39] 0 0
Italy
State/province [39] 0 0
Meldola
Country [40] 0 0
Italy
State/province [40] 0 0
Milano
Country [41] 0 0
Italy
State/province [41] 0 0
Padova
Country [42] 0 0
Italy
State/province [42] 0 0
Roma
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Pusan
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Seongnam-si
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Seoul
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Suwon-si
Country [47] 0 0
Portugal
State/province [47] 0 0
Lisboa
Country [48] 0 0
Portugal
State/province [48] 0 0
Almada
Country [49] 0 0
Portugal
State/province [49] 0 0
Coimbra
Country [50] 0 0
Portugal
State/province [50] 0 0
Lisbon
Country [51] 0 0
Portugal
State/province [51] 0 0
Porto
Country [52] 0 0
Puerto Rico
State/province [52] 0 0
Rio Piedras
Country [53] 0 0
Spain
State/province [53] 0 0
Andalucia
Country [54] 0 0
Spain
State/province [54] 0 0
Aragon
Country [55] 0 0
Spain
State/province [55] 0 0
Castilla Y Leon
Country [56] 0 0
Spain
State/province [56] 0 0
Cataluna
Country [57] 0 0
Spain
State/province [57] 0 0
Barcelona
Country [58] 0 0
Spain
State/province [58] 0 0
Madrid
Country [59] 0 0
Spain
State/province [59] 0 0
Valencia
Country [60] 0 0
Taiwan
State/province [60] 0 0
Tainan
Country [61] 0 0
Taiwan
State/province [61] 0 0
Huwei
Country [62] 0 0
Taiwan
State/province [62] 0 0
Kaohsiung
Country [63] 0 0
Taiwan
State/province [63] 0 0
Taichung City
Country [64] 0 0
Taiwan
State/province [64] 0 0
Taipei
Country [65] 0 0
Taiwan
State/province [65] 0 0
Taoyuan City
Country [66] 0 0
Thailand
State/province [66] 0 0
Songkla
Country [67] 0 0
Thailand
State/province [67] 0 0
Bangkok
Country [68] 0 0
Thailand
State/province [68] 0 0
Chiang Mai
Country [69] 0 0
Thailand
State/province [69] 0 0
Khon Kaen
Country [70] 0 0
Thailand
State/province [70] 0 0
Phitsanulok
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Nottinghamshire
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Surrey
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Wirral
Country [74] 0 0
United Kingdom
State/province [74] 0 0
London
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
QED Therapeutics, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Helsinn Healthcare SA
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03773302