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

Sponsor

QED Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03773302

Collaborator

Helsinn Healthcare SA (Industry)

300

Enrollment

131

Locations

Arms

84.1

Anticipated Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cholangiocarcinoma FGFR2 Gene Mutation	Drug: BGJ398 Drug: Gemcitabine Drug: Cisplatin	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Dec 27, 2019

Anticipated Primary Completion Date :

Jan 30, 2026

Anticipated Study Completion Date :

Dec 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Infigratinib (BGJ398) 125 mg Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.	Drug: BGJ398 Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off. Other Names: Infigratinib
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.	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.

Arm

Intervention/Treatment

Experimental: Infigratinib (BGJ398) 125 mg

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Drug: BGJ398

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Other Names:

Infigratinib

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.

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.

Outcome Measures

Primary Outcome Measures

Progression-free survival (central imaging assessment) [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.

Secondary Outcome Measures

Overall survival in participants treated with infigratinib versus gemcitabine with cisplatin [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 [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. [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. [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. [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. [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. [Approximately from baseline to last dose date of study treatment + 30 days, approximately 12 months on average]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Exclusion Criteria:

Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma, with following exceptions

Prior neoadjuvant or adjuvant therapy is permitted if completed > 6 months after the last dose of neoadjuvant or adjuvant therapy.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	University of Arizona	Tucson	Arizona	United States	85724
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Chang Soon-Shiong Institute for Medicine	El Segundo	California	United States	92868
5	St. Joseph Heritage Healthcare	Fullerton	California	United States	92835
6	Scripps Clinic	La Jolla	California	United States	92037
7	Loma Linda University	Loma Linda	California	United States	92354
8	The Oncology Institute of Hope and Innovation	Long Beach	California	United States	90805
9	USC Norris Cancer Center	Los Angeles	California	United States	90033
10	University of California Los Angeles	Los Angeles	California	United States	90095
11	Desert Regional Medical Center	Palm Springs	California	United States	92262
12	Pacific Hematology Oncology Associates	San Francisco	California	United States	94115
13	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
14	Miami Cancer Institute	Miami	Florida	United States	33176
15	Florida Hospital Medical Group	Orlando	Florida	United States	32804
16	UF Health Cancer Center at Orlando Health	Orlando	Florida	United States	32806
17	Piedmont Cancer Institute	Atlanta	Georgia	United States	30318
18	Illinois Cancer Specialists (Arlington Heights)	Arlington Heights	Illinois	United States	60005
19	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
20	Carle Cancer Center	Urbana	Illinois	United States	61801
21	University of Louisville	Louisville	Kentucky	United States	40202
22	University Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
23	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
24	Frederick Regional Healthcare Systems/James M. Stockman Cancer Institute	Frederick	Maryland	United States	21702
25	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
26	Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center	Detroit	Michigan	United States	48201
27	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan	United States	49503
28	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
29	Minnesota Oncology Hematology	Minneapolis	Minnesota	United States	55404
30	Atlantic Health System	Summit	New Jersey	United States	07901
31	Bruckner Oncology	Bronx	New York	United States	10469
32	NYU Langone Medical Center	New York	New York	United States	10016
33	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
34	Levine Cancer Institute - Charlotte	Charlotte	North Carolina	United States	28204
35	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
36	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43202
37	Northwest Cancer Specialists	Portland	Oregon	United States	97227
38	Allegheny Singer Research Institute	Pittsburgh	Pennsylvania	United States	15212
39	Charleston Oncology	Charleston	South Carolina	United States	29414
40	Parkland Health and Hospital System	Dallas	Texas	United States	75343
41	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
42	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
43	Baylor College of Medicine	Houston	Texas	United States	77096
44	Texas Oncology	Tyler	Texas	United States	75702
45	Chris O'Brien Lifehouse Hospital	Camperdown	New South Wales	Australia
46	Blacktown Hospital	Darlinghurst	New South Wales	Australia
47	Royal Adelaide Hospital	Adelaide	South Australia	Australia
48	Monash Medical Centre	Bentleigh East	Victoria	Australia
49	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria	Australia
50	St John of God Hospital Subiaco	Subiaco	Western Australia	Australia
51	Cliniques Universitaires Saint-Luc	Bruxelles	Brussels	Belgium	1200
52	Grand Hopital de Charleroi	Charleroi		Belgium	6000
53	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
54	Cross Cancer Institute	Edmonton	Alberta	Canada
55	Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
56	St. Josephs Health Centre	Toronto	Ontario	Canada
57	Jewish General Hospital	Montréal	Quebec	Canada	H3T 1E2
58	Beijing Cancer Hospital	Beijing		China	100142
59	Guangzhou First People's Hospital	Guangzhou		China	510080
60	Hubei Cancer Hospital	Hubei		China	430079
61	Hopital Henri Mondor	Créteil	Val-de-Marne	France	94000
62	CHRU Dijon	Dijon		France	21000
63	Centre Georges-Francois Leclerc	Dijon		France	21079
64	Hopital Claude Huriez Rue Michel Polonovski (CHRU) Lille	Lille		France	59000
65	Groupement Hospitalier Edouard Herriot	Lyon		France	69437
66	Hopital Nord Franche-Comte	Montbéliard		France	25200
67	Groupe Hospitalier Archet I Et II	Nice		France	06202
68	Hopital Cochin	Paris		France	75014
69	Hôpital Saint Antoine	Paris		France	75571
70	L'Institut Mutualiste Montsouris	Paris		France	75674
71	Universitätsklinikum Tübingen	Tübingen	Baden-Wurttemberg	Germany	72076
72	Klinikum rechts der Isar der Technischen Universität München	München	Bayern	Germany	81675
73	Klinikum Dortmund gGmbH	Dortmund		Germany	44137
74	University Clinic Heidelberg	Heidelberg		Germany	69120
75	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena	Emilia-Romagna	Italy	41100
76	Azienda Socio Sanitaria Territoriale di Cremona (ASST)	Cremona		Italy	26100
77	Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST	Meldola		Italy	47014
78	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
79	ASST Grande Ospedale Metropolitano Niguarda	Milano		Italy	20162
80	Istituto Oncologico Veneto - I.R.C.C.S.	Padova		Italy	35128
81	Policlinico Universitario Campus Biomedico Di Roma	Roma		Italy	00128
82	Pusan National University Hospital	Pusan		Korea, Republic of
83	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of
84	SMG - SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
85	Samsung Medical Center	Seoul		Korea, Republic of
86	Seoul National University Hospital	Seoul		Korea, Republic of
87	Severance Hospital Yonsei University Health System	Seoul		Korea, Republic of
88	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of
89	Ajou University Hospital	Suwon-si		Korea, Republic of
90	Hospital Beatriz Angelo	Loures	Lisboa	Portugal	2674-514
91	Hospital Garcia de Orta	Almada		Portugal	2801-951
92	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra		Portugal	3000-075
93	Instituto Português de Oncologia Francisco Gentil Centro Regional de Oncologia de Coimbra EPE	Coimbra		Portugal	3000-075
94	Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria	Lisboa		Portugal	1649-035
95	Hospital CUF Descobertas	Lisboa		Portugal	1998-018
96	Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.	Lisbon		Portugal	1099-023
97	Centro Hospitalar do Porto - Hospital de Santo António	Porto		Portugal	4099-001
98	Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS	Porto		Portugal	4200-072
99	Centro Hospitalar de São João, E.P.E.	Porto		Portugal	4200-319
100	Hospital Oncologico, Puerto Rico Medical Center	Rio Piedras		Puerto Rico	00935
101	Hospital Universitario Virgen Macarena	Sevilla	Andalucia	Spain	41009
102	Hospital Universitario Miguel Servet	Zaragoza	Aragon	Spain	50009
103	Complejo Asistencial Universitario de Salamanca - Hospital Clinico	Salamanca	Castilla Y Leon	Spain	37007
104	Hospital Universitario Germans Trias i Pujol	Badalona	Cataluna	Spain	08916
105	Instituto Catalan de Oncologio ICO I'Hospitalet	Barcelona	Cataluna	Spain	08907
106	Hospital Universitario Vall d'Hebrón - PPDS	Barcelona		Spain	08035
107	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
108	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
109	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
110	Hospital Universitario La Paz	Madrid		Spain	28046
111	Hospital Universitario HM Sanchinarro - CIOCC	Madrid		Spain	28050
112	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
113	National Cheng Kung University Hospital	Tainan City	Tainan	Taiwan	704
114	National Taiwan University Hospital - YunLin Branch	Huwei		Taiwan	632
115	Chang Gung Memorial Hospital - Kaohsiung	Kaohsiung		Taiwan	833
116	China Medical University Hospital	Taichung City		Taiwan	40447
117	Chi Mei Hospital, Liouying	Tainan		Taiwan	73657
118	Taipei Veterans General Hospital	Taipei		Taiwan	11217
119	National Taiwan University Hospital	Taipei		Taiwan
120	Chang Gung Memorial Hospital, Linkou	Taoyuan City		Taiwan	333
121	Songklanagarind Hospital, Prince of Songkla University	Hat Yai	Songkla	Thailand	90110
122	Chulalongkorn University	Bangkok		Thailand	10330
123	Ramathibodi Hospital Mahidol University	Bangkok		Thailand
124	Maharaj Nakorn Chiang Mai Chiang Mai University	Chiang Mai		Thailand	50200
125	Srinagarind Hospital	Khon Kaen		Thailand
126	Naresuan University	Phitsanulok		Thailand
127	Nottingham City Hospital	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
128	Royal Marsden Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
129	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Wirral	United Kingdom	CH63 4JY
130	Guys Hospital	London		United Kingdom	SE1 9RT
131	The Christie NHS Foundation Trust - PPDS	Manchester		United Kingdom	M20 4BX