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

Advanced Cholangiocarcinoma Clinical Trial

— FOENIX-CCA3  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04093362
• Other study ID #: TAS-120-301
• Secondary ID: 2019-004630-42
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 1, 2020
• Est. completion date: June 2024

Study information

• Verified date: January 2024
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 216
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for enrollment

in this study:

1. Provide written informed consent.

2. Is =18 years of age (or meets the country's regulatory definition for legal adult age).

3. 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.

4. Patient has radiographically measurable disease per RECIST 1.1.

5. 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.

6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.

7. 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

8. 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.

9. 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:

1. Patient has received previous systemic anticancer therapy.

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

2. Patient has mixed hepatocellular carcinoma - iCCA disease.

3. 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.

4. History or current evidence of uncontrolled ventricular arrhythmias

5. Fridericia's corrected QT interval (QTcF) > 470 ms on electrocardiogram (ECG) conducted during Screening.

6. 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.

7. 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.

8. Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention.

9. Pregnant or breast-feeding female.

10. The patient is unable to take oral medication.

Related Conditions & MeSH terms

• Advanced Cholangiocarcinoma
• Cholangiocarcinoma
• FGFR2 Gene Rearrangements

Intervention

Drug:
• TAS-120
TAS-120 is an oral FGFR inhibitor
• Cisplatin/Gemcitabine
Cisplatin/Gemcitabine is currently 1st line standard of care

Locations

Country	Name	City	State
Argentina	Fundacion Favaloro para la Docencia e Investigacion Medica	Buenos Aires	Caba
Argentina	Hospital de Gastroenterologia Dr. C. Bonorino Udaondo	Buenos Aires	Caba
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Newcastle Private Hospital	Newcastle	New South Wales
Belgium	UZ Antwerpen	Edegem	Antwerpen
Belgium	CHC MontLégia	Liège	Liege
Belgium	Algemeen Ziekenhuis AZ Sint-Maarten	Mechelen	Antwerpen
Belgium	AZ Delta Roeselare	Roeselare	Flemish Region
Brazil	IOP - Instituto de Oncologia do Parana	Curitiba	PR
Brazil	Instituto Americas	Rio De Janeiro	RJ
Brazil	Instituto Nacional de Cancer Jose Alencar Gomes da Silva - INCA	Rio De Janeiro	RJ
Brazil	Cepho-Fm Abc	Santo Andre	SP
Brazil	Hospital de Base de Sao Jose do Rio Preto	São José Do Rio Preto	SP
Brazil	Fundacao Antonio Prudente - A.C.Camargo Cancer Center	São Paulo	SP
Brazil	Hospital Municipal Vila Santa Catarina	São Paulo	SP
Brazil	Hospital Santa Marcelina HSM	São Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo	São Paulo	SP
France	Hopitaux Universitaires Paris Nord Val de Seine - Hopital Beaujon	Clichy
France	Centre Georges-Francois Leclerc	Dijon
France	Centre Hospitalier Universitaire de Grenoble	La Tronche
France	Centre Leon Berard	Lyon
France	CHRU Besancon	Montbéliard
France	CHU Reims	Reims
France	Institut de Cancerologie Strasbourg Europe ICAENS	Strasbourg
France	CHU de TOURS - Hopital Trousseau	Tours
Germany	Charite - Universitaetsmedizin Berlin	Berlin
Germany	Universitaetsmedizin Mainz	Mainz
Germany	Technische Universitaet Muenchen - Klinikum rechts der Isar	Muenchen
Hong Kong	The University of Hong Kong, Queen Mary Hospital	Hong Kong
Hong Kong	The Chinese University of Hong Kong Prince of Wales Hospital	Shatin
Italy	Candiolo Cancer Institute - FPO IRCCS	Candiolo
Italy	Ospedale Versilia	Lucca
Italy	AOU di Cagliari	Monserrato
Italy	Ospedale Maggiore della Carita di Novara	Novara
Italy	Servizio Sanitario Regionale Emilia-Romagna - Azienda Ospedaliero-Universitaria di Parma Ospedale Maggiore	Parma
Italy	Policlinico Uni. Campus Bio-Medico	Roma
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena
Italy	AOUI Verona - Ospedale Borgo Roma	Verona
Italy	Azienda ULSS 8 Berica	Vicenza
Japan	Chiba University Hospital	Chiba-shi	Chiba
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa-Shi	Chiba
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo
Japan	Kyorin University Hospital	Mitaka-shi	Tokyo
Japan	Nagasaki University Hospital	Nagasaki-shi	Nagasaki
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Osaka city University Hospital	Osaka-shi	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Osaka University Hospital	Suita-shi	Osaka
Japan	Kanagawa Cancer Center	Yokohama-Shi	Kanagawa
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-Do
Korea, Republic of	Seoul National University Hospital	Jungni I Gu	Seoul
Korea, Republic of	CHA Bundang Medical Center	Seongnam
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Korea, Republic of	Asan Medical Center	Seul	Seoul
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City	MX
Mexico	Hospital Universitario Jose Eleuterio Gonzalez	Monterrey	Nuevo Leon
Mexico	Centro de Estudios y Prevencion del Cancer (CEPREC)	Tuxtla Gutiérrez	Chiapas
Netherlands	Radboud University Medical Center	Nijmegen	GA
Peru	Hospital Goyeneche	Arequipa
Peru	Hospital Daniel Alcides Carrion	Bellavista	Callao
Peru	Hospital Nacional Arzobispo Loayza	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas (INEN)	Surquillo	Lima
Poland	Centrum Medyczne HCP Sp. z o.o.	Poznan	Wielkopolskie
Poland	Szpital Kliniczny Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu	Poznan	Woj. Wielkopolskie
Portugal	Fundacao Champalimaud	Lisboa
Portugal	CUF Porto Hospital	Porto
Portugal	Instituto Portugues de Oncologia do Porto	Porto
Spain	Onkologikoa	Donostia-San Sebastian	Gipuzkoa
Spain	Hospital Universitario Virgen de la Arrixaca HUVA	El Palmar	Murcia
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Taiwan	Chang Gung Memorial Hospital CGMH - Kaohsiung Branch	Kaohsiung
Taiwan	Chang Gung Memorial Hospital, Linkou	Taichung
Taiwan	Chi Mei Medical Center CMMC - Yongkang branch	Tainan
Taiwan	National Cheng Kung University Hospital NCKUH	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Thailand	Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy	Bangkok
Thailand	Rajavithi hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University	ChiangMai
Thailand	Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University	Hat Yai	Songkhla
Thailand	Khon Kaen University KKU - Faculty of Medicine-Srinagarind Hospital	Khon Kaen	Muang
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	University College London Hospital NHS Foundation Trust	London
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	City of Hope National Medical Center	Duarte	California
United States	Norton Cancer Institute Audubon Hospital Campus Medical Plaza	Louisville	Kentucky
United States	Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Medical College of Wisconsin - Froedtert Hospital	Milwaukee	Wisconsin
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Medical Oncology Associates, PS - Summit Cancer Centers	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Poland,  Portugal,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors	up to 12 months
Secondary	ORR	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.	up to12 months
Secondary	DCR	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.	up to 12 months
Secondary	OS	defined as the time from the date of randomization until the date of death due to any cause.	up to 12 months
Secondary	PFS per Investigator assessment	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	up to 12 months
Secondary	Safety and Tolerability	Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs)	up to 12 months