FOENIX-CCA3: Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements

Sponsor

Taiho Oncology, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04093362

Collaborator

(none)

216

Enrollment

104

Locations

Arms

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, multinational, parallel 2-arm, randomized Phase 3 study evaluating the efficacy and safety of futibatinib versus gemcitabine-cisplatin chemotherapy as first-line treatment of patients with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements

Condition or Disease	Intervention/Treatment	Phase
Advanced Cholangiocarcinoma FGFR2 Gene Rearrangements	Drug: TAS-120 Drug: Cisplatin/Gemcitabine	Phase 3

Detailed Description

Study TAS-120-301 is an open-label, multinational, parallel 2-arm, randomized Phase 3 study evaluating the efficacy and safety of futibatinib versus gemcitabine-cisplatin chemotherapy as first-line treatment of patients with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements. Eligible patients will be randomized on a 1:1 basis to the following study arms:

Experimental Arm: Patients will receive futibatinib at an oral dose of 20 mg, administered daily (QD) on every day of a 21-day cycle.
Control Arm: On Days 1 and 8 of a 21-day cycle, patients will receive:
Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (I.V.) infusion over 1 hour, followed by 500 mL 0.9% saline over 30 minutes; and
Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by I.V. infusion over 30 minutes, beginning after completion of the cisplatin and saline infusions.

Patients in the Experimental Arm may continue to receive continuous futibatinib until documentation of progressive disease (PD) per RECIST 1.1, or until other withdrawal criteria are met, whichever comes first. However, treatment may continue following PD per RECIST 1.1 if the patient is clinically stable and is considered by the Investigator to be deriving continued clinical benefit from futibatinib.

Patients in the Control Arm may receive gemcitabine-cisplatin chemotherapy for up to 8 cycles or until PD or other withdrawal criteria are met, whichever comes first. Patients who discontinue gemcitabine-cisplatin due to documented disease progression (by ICR) may receive treatment with futibatinib ("crossover"), if medically appropriate in the opinion of the Investigator and if criteria for futibatinib treatment are met.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

216 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Open-Label, Randomized Study of Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements FOENIX-CCA3

Actual Study Start Date :

Mar 1, 2020

Anticipated Primary Completion Date :

Apr 1, 2027

Anticipated Study Completion Date :

Apr 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAS-120 TAS-120 tablets, oral; 21-day cycle	Drug: TAS-120 TAS-120 is an oral FGFR inhibitor Other Names: Futibatinib
Active Comparator: Cisplatin/Gemcitabine • On Days 1 and 8 of a 21-day cycle, patients will receive: Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (I.V.) infusion over 1 hour, followed by 500 mL 0.9% saline over 30 minutes; and Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by I.V. infusion over 30 minutes, beginning after completion of the cisplatin and saline infusions.	Drug: Cisplatin/Gemcitabine Cisplatin/Gemcitabine is currently 1st line standard of care

Arm

Intervention/Treatment

Experimental: TAS-120

TAS-120 tablets, oral; 21-day cycle

Drug: TAS-120

TAS-120 is an oral FGFR inhibitor

Other Names:

Futibatinib

Active Comparator: Cisplatin/Gemcitabine

• On Days 1 and 8 of a 21-day cycle, patients will receive: Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (I.V.) infusion over 1 hour, followed by 500 mL 0.9% saline over 30 minutes; and Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by I.V. infusion over 30 minutes, beginning after completion of the cisplatin and saline infusions.

Drug: Cisplatin/Gemcitabine

Cisplatin/Gemcitabine is currently 1st line standard of care

Outcome Measures

Primary Outcome Measures

PFS: defined as the time from date of randomization to the date of documentation of disease progression by ICR per RECIST (version 1.1, 2009) or date of death, whichever comes first. [up to 12 months]
Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors

Secondary Outcome Measures

ORR [up to12 months]
defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST 1.1), based on ICR.
DCR [up to 12 months]
defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST 1.1), based on ICR.
OS [up to 12 months]
defined as the time from the date of randomization until the date of death due to any cause.
PFS per Investigator assessment [up to 12 months]
defined as the time from date of randomization to the date of disease progression based on Investigator assessment of radiographic images or death, whichever occurs first
Safety and Tolerability [up to 12 months]
Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study:

Provide written informed consent.
Is ≥18 years of age (or meets the country's regulatory definition for legal adult age).
The patient has histologically confirmed, locally advanced, or metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements based on testing performed by the designated central laboratory.
Patient has radiographically measurable disease per RECIST 1.1.
Patients who have received treatment for locally advanced disease (for example, trans-arterial chemoembolization, selective internal radiation therapy, external beam radiation) must have evidence of radiographic progression with measurable disease outside the previously-treated lesions.
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
Adequate organ function as defined by the following criteria:

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤ 5 × ULN.
Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert's syndrome.
White Blood Count (WBC) ≥ 2000/mm3 (≥ 2.0 × 109/L)
Absolute neutrophil count (ANC) ≥ 1000/mm3 (ie, ≥ 1.0 × 109/L by International Units [IU])
Platelet count ≥ 100,000/mm3 (IU: ≥ 100 × 109/L)
Hemoglobin ≥ 9.0 g/dL
Phosphorus ≤ 1.5 × ULN
Creatinine clearance: ≥ 60 mL/min

Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of the first dose of futibatinib. Female patients are not considered to be of child bearing potential if they have a history of hysterectomy or are post menopausal defined as no menses for 12 months without an alternative medical cause. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose and for 6 months after the last dose.
Willing and able to comply with scheduled visits and study procedures.

Exclusion Criteria:

A patient will be excluded from this study if any of the following criteria are met:

Patient has received previous systemic anticancer therapy.

• Patients receiving adjuvant or neoadjuvant treatment and completed ≥6 months prior to randomization are eligible.

Patient has mixed hepatocellular carcinoma - iCCA disease.
History and/or current evidence of any of the following disorders:

Non-tumor related alteration of calcium-phosphorus homeostasis that is clinically significant in the opinion of the Investigator.
Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator.
Retinal disorder confirmed by retinal examination and considered clinically significant in the opinion of the ophthalmologist.

History or current evidence of uncontrolled ventricular arrhythmias
Fridericia's corrected QT interval (QTcF) > 470 ms on electrocardiogram (ECG) conducted during Screening.
Treatment with any of the following within the specified time frame prior to the first dose of study therapy, or failure to recover from side effects of these prior therapies:

Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of study therapy).
Radiotherapy (any dose) for extended field within 4 weeks or limited field radiotherapy within 2 weeks, and/or has not recovered from acute impact of radiotherapy.
Patients with locoregional therapy, e.g. transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks.
Any history of liver transplant.

A serious illness or medical condition(s) including, but not limited to, the following:

Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month).
Known acute systemic infection.
Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months.
Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the Investigator.
Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the Investigator would make the patient inappropriate for entry into this study.

Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention.
Pregnant or breast-feeding female.
The patient is unable to take oral medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	Norton Cancer Institute Audubon Hospital Campus Medical Plaza	Louisville	Kentucky	United States	40217
3	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87131
4	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
5	University of vigninia cancer center	Charlottesville	Virginia	United States	22908
6	Medical Oncology Associates, PS - Summit Cancer Centers	Spokane	Washington	United States	99208
7	Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
8	Medical College of Wisconsin - Froedtert Hospital	Milwaukee	Wisconsin	United States	53226
9	Fundacion Favaloro para la Docencia e Investigacion Medica	Buenos Aires	Caba	Argentina	C1093
10	Hospital de Gastroenterologia Dr. C. Bonorino Udaondo	Buenos Aires	Caba	Argentina	CP1264
11	Newcastle Private Hospital	Newcastle	New South Wales	Australia	2305
12	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
13	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3002
14	UZ Antwerpen	Edegem	Antwerpen	Belgium	2650
15	Algemeen Ziekenhuis AZ Sint-Maarten	Mechelen	Antwerpen	Belgium	2800
16	AZ Delta Roeselare	Roeselare	Flemish Region	Belgium	8800
17	CHC MontLégia	Liège	Liege	Belgium	4000
18	IOP - Instituto de Oncologia do Parana	Curitiba	PR	Brazil	80520-174
19	Instituto Nacional de Cancer Jose Alencar Gomes da Silva - INCA	Rio De Janeiro	RJ	Brazil	20231-050
20	Instituto Americas	Rio De Janeiro	RJ	Brazil	22775-001
21	Cepho-Fm Abc	Santo Andre	SP	Brazil	09060-650
22	Hospital de Base de Sao Jose do Rio Preto	São José Do Rio Preto	SP	Brazil	15090-000
23	Instituto do Cancer do Estado de Sao Paulo	São Paulo	SP	Brazil	01246-000
24	Fundacao Antonio Prudente - A.C.Camargo Cancer Center	São Paulo	SP	Brazil	01509-010
25	Hospital Municipal Vila Santa Catarina	São Paulo	SP	Brazil	04377-035
26	Hospital Santa Marcelina HSM	São Paulo	SP	Brazil	08270-120
27	Hopitaux Universitaires Paris Nord Val de Seine - Hopital Beaujon	Clichy		France	92110
28	Centre Georges-Francois Leclerc	Dijon		France	21000
29	Centre Hospitalier Universitaire de Grenoble	La Tronche		France	38700
30	Centre Leon Berard	Lyon		France	69008
31	CHRU Besancon	Montbéliard		France	25 200
32	CHU Reims	Reims		France	51092
33	Institut de Cancerologie Strasbourg Europe ICAENS	Strasbourg		France	67033
34	CHU de TOURS - Hopital Trousseau	Tours		France	37044
35	Charite - Universitaetsmedizin Berlin	Berlin		Germany	13353
36	Universitaetsmedizin Mainz	Mainz		Germany	55131
37	Technische Universitaet Muenchen - Klinikum rechts der Isar	Muenchen		Germany	Muenchen
38	The University of Hong Kong, Queen Mary Hospital	Hong Kong		Hong Kong	2255-4249
39	The Chinese University of Hong Kong Prince of Wales Hospital	Shatin		Hong Kong
40	Candiolo Cancer Institute - FPO IRCCS	Candiolo		Italy
41	Ospedale Versilia	Lucca		Italy	555041
42	AOU di Cagliari	Monserrato		Italy	9042
43	Ospedale Maggiore della Carita di Novara	Novara		Italy	28100
44	Servizio Sanitario Regionale Emilia-Romagna - Azienda Ospedaliero-Universitaria di Parma Ospedale Maggiore	Parma		Italy	43126
45	Policlinico Uni. Campus Bio-Medico	Roma		Italy	12800
46	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena		Italy	53100
47	AOUI Verona - Ospedale Borgo Roma	Verona		Italy	37134
48	Azienda ULSS 8 Berica	Vicenza		Italy	36100
49	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
50	Chiba University Hospital	Chiba-shi	Chiba	Japan	260-8677
51	National Cancer Center Hospital East	Kashiwa-Shi	Chiba	Japan	277-8577
52	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka	Japan	811-1395
53	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
54	Kanagawa Cancer Center	Yokohama-Shi	Kanagawa	Japan	241-8515
55	Nagasaki University Hospital	Nagasaki-shi	Nagasaki	Japan	852-8501
56	Osaka city University Hospital	Osaka-shi	Osaka	Japan	545-8586
57	Osaka University Hospital	Suita-shi	Osaka	Japan	565-0871
58	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
59	The Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo	Japan	135-8550
60	Kyorin University Hospital	Mitaka-shi	Tokyo	Japan	181-8611
61	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-Do	Korea, Republic of	58128
62	Seoul National University Hospital	Jungni I Gu	Seoul	Korea, Republic of	3080
63	Asan Medical Center	Seul	Seoul	Korea, Republic of	5505
64	Dong-A University Hospital	Busan		Korea, Republic of	49201
65	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
66	Gyeongsang National University Hospital	Jinju		Korea, Republic of	52727
67	CHA Bundang Medical Center	Seongnam		Korea, Republic of	13496
68	Yonsei University Health System - Severance Hospital	Seoul		Korea, Republic of	3722
69	Samsung Medical Center	Seoul		Korea, Republic of	6351
70	Centro de Estudios y Prevencion del Cancer (CEPREC)	Tuxtla Gutiérrez	Chiapas	Mexico	29038
71	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City	MX	Mexico	14080
72	Hospital Universitario Jose Eleuterio Gonzalez	Monterrey	Nuevo Leon	Mexico	64460
73	Radboud University Medical Center	Nijmegen	GA	Netherlands	6525
74	Hospital Daniel Alcides Carrion	Bellavista	Callao	Peru	07016
75	Instituto Nacional de Enfermedades Neoplasicas (INEN)	Surquillo	Lima	Peru	15038
76	Hospital Goyeneche	Arequipa		Peru	04001
77	Hospital Nacional Arzobispo Loayza	Lima		Peru	15082
78	Centrum Medyczne HCP Sp. z o.o.	Poznań	Wielkopolskie	Poland	61-485
79	Szpital Kliniczny Przemienienia Pańskiego UM im. Karola Marcinkowskiego w Poznaniu	Poznań	Woj. Wielkopolskie	Poland	60-569
80	Fundacao Champalimaud	Lisboa		Portugal	1400-038
81	CUF Porto Hospital	Porto		Portugal	4100-180
82	Instituto Portugues de Oncologia do Porto	Porto		Portugal	4200-072
83	Onkologikoa	Donostia-San Sebastian	Gipuzkoa	Spain	20014
84	Hospital Universitario Virgen de la Arrixaca HUVA	El Palmar	Murcia	Spain	30120
85	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
86	Clinica Universidad de Navarra	Madrid		Spain	28022
87	MD Anderson Cancer Center	Madrid		Spain	28033
88	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
89	Hospital Universitario 12 de Octubre	Madrid		Spain	28043
90	Clinica Universidad de Navarra	Pamplona		Spain
91	Chang Gung Memorial Hospital CGMH - Kaohsiung Branch	Kaohsiung		Taiwan	83301
92	Chang Gung Memorial Hospital, Linkou	Taichung		Taiwan	40447
93	National Cheng Kung University Hospital NCKUH	Tainan		Taiwan	704
94	Chi Mei Medical Center CMMC - Yongkang branch	Tainan		Taiwan	710
95	National Taiwan University Hospital	Taipei		Taiwan	10002
96	Taipei Veterans General Hospital	Taipei		Taiwan	11217
97	Khon Kaen University KKU - Faculty of Medicine-Srinagarind Hospital	Khon Kaen	Muang	Thailand	40002
98	Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University	Hat Yai	Songkhla	Thailand	90110
99	Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy	Bangkok		Thailand	10210
100	Rajavithi hospital	Bangkok		Thailand	10400
101	Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University	ChiangMai		Thailand	50200
102	University Hospitals Bristol NHS Foundation Trust	Bristol		United Kingdom	BS2 8ED
103	University College London Hospital NHS Foundation Trust	London		United Kingdom	NW1 2PG
104	Royal Free London NHS Foundation Trust	London		United Kingdom	NW3 2QG