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

NCT04093362 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: TAS-120-3012019-004630-42
• Study Type: interventional
• Target: 10
• Locations: 20 countries
• Sites: 103

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 participants with advanced, metastatic, or recurrent unresectable intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene rearrangements

Conditions

Advanced Cholangiocarcinoma; FGFR2 Gene Rearrangements

Keywords

Futibatinib; Advanced Cholangiocarcinoma; FGFR2; Fusion; Rearrangement; TAS-120

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS was defined as the time from date of randomization to the date of documentation of disease progression by independent central review (ICR), or date of death, whichever occurs first. Response assessments were made based on Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009)

  Up to approximately 28 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to approximately 28 months

• Disease Control Rate (DCR)

  Up to approximately 28 months

• Overall Survival (OS)

  Up to approximately 28 months

• Progression-Free Survival (PFS) Per Investigator Assessment

  Up to approximately 28 months

• Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs)

  Up to approximately 28 months

Study Arms (2)

Futibatinib

EXPERIMENTAL

Participants received futibatinib at an oral dose of 20 milligrams (mg), administered once daily (QD) on every day of a 21-day cycle up to disease progression.

Drug: Futibatinib

Cisplatin/Gemcitabine

ACTIVE COMPARATOR

Participants received cisplatin 25 milligrams per square meter (mg/m\^2) IV infusion followed by gemcitabine 1000 mg/m\^2 IV infusion on Days 1 and 8 of each 21-day cycle up to 8 cycles.

Drug: Cisplatin; Drug: Gemcitabine

Interventions

Futibatinib DRUG

Oral tablets

Also known as: TAS-120

Futibatinib

Cisplatin DRUG

IV infusion

Cisplatin/Gemcitabine

Gemcitabine DRUG

IV infusion

Cisplatin/Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent.
• Is ≥18 years of age (or meets the country's regulatory definition for legal adult age).
• The participant has histologically confirmed, locally advanced, or metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements based on testing performed by the designated central laboratory.
• Participant has radiographically measurable disease per RECIST 1.1.
• Participants 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 participants 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

You may not qualify if:

• A participant will be excluded from this study if any of the following criteria are met:
• Participant has received previous systemic anticancer therapy.
• Participants receiving adjuvant or neoadjuvant treatment and completed ≥6 months prior to randomization are eligible.
• Participant 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 milliseconds (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.
• Participants with locoregional therapy, e.g. transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks.
• Any history of liver transplant.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (103)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Norton Cancer Institute Audubon Hospital Campus Medical Plaza

Louisville, Kentucky, 40217, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87131, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Medical Oncology Associates, PS - Summit Cancer Centers

Spokane, Washington, 99208, United States

Location

Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Fundacion Favaloro para la Docencia e Investigacion Medica

Buenos Aires, Buenos Aires F.D., C1093, Argentina

Location

Hospital de Gastroenterologia Dr. C. Bonorino Udaondo

Buenos Aires, Buenos Aires F.D., CP1264, Argentina

Location

Newcastle Private Hospital

Newcastle, New South Wales, 2305, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

UZ Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

Algemeen Ziekenhuis AZ Sint-Maarten

Mechelen, Antwerpen, 2800, Belgium

Location

AZ Delta Roeselare

Roeselare, Flanders, 8800, Belgium

Location

CHC MontLégia

Liège, Liege, 4000, Belgium

Location

IOP - Instituto de Oncologia do Parana

Curitiba, Paraná, 80520-174, Brazil

Location

Instituto Nacional de Cancer Jose Alencar Gomes da Silva - INCA

Rio de Janeiro, Rio de Janeiro, 20231-050, Brazil

Location

Instituto Americas

Rio de Janeiro, Rio de Janeiro, 22775-001, Brazil

Location

Cepho-Fm Abc

Santo André, São Paulo, 09060-650, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, 01246-000, Brazil

Location

Fundacao Antonio Prudente - A.C.Camargo Cancer Center

São Paulo, São Paulo, 01509-010, Brazil

Location

Hospital Municipal Vila Santa Catarina

São Paulo, São Paulo, 04377-035, Brazil

Location

Hospital Santa Marcelina HSM

São Paulo, São Paulo, 08270-120, Brazil

Location

Hopitaux Universitaires Paris Nord Val de Seine - Hopital Beaujon

Clichy, 92110, France

Location

Centre Georges-Francois Leclerc

Dijon, 21000, France

Location

Centre Hospitalier Universitaire de Grenoble

La Tronche, 38700, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

CHRU Besancon

Montbéliard, 25 200, France

Location

CHU Reims

Reims, 51092, France

Location

Institut de Cancerologie Strasbourg Europe ICAENS

Strasbourg, 67033, France

Location

CHU de TOURS - Hopital Trousseau

Tours, 37044, France

Location

Charite - Universitaetsmedizin Berlin

Berlin, 13353, Germany

Location

Universitaetsmedizin Mainz

Mainz, 55131, Germany

Location

Technische Universitaet Muenchen - Klinikum rechts der Isar

München, Muenchen, Germany

Location

The University of Hong Kong, Queen Mary Hospital

Hong Kong, 2255-4249, Hong Kong

Location

The Chinese University of Hong Kong Prince of Wales Hospital

Shatin, Hong Kong

Location

Candiolo Cancer Institute - FPO IRCCS

Candiolo, Italy

Location

Ospedale Versilia

Lucca, 555041, Italy

Location

AOU di Cagliari

Monserrato, 9042, Italy

Location

Ospedale Maggiore della Carita di Novara

Novara, 28100, Italy

Location

Servizio Sanitario Regionale Emilia-Romagna - Azienda Ospedaliero-Universitaria di Parma Ospedale Maggiore

Parma, 43126, Italy

Location

Policlinico Uni. Campus Bio-Medico

Roma, 12800, Italy

Location

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, 53100, Italy

Location

AOUI Verona - Ospedale Borgo Roma

Verona, 37134, Italy

Location

Azienda ULSS 8 Berica

Vicenza, 36100, Italy

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Chiba University Hospital

Chiba, Chiba, 260-8677, Japan

Location

National Cancer Center Hospital East

Kashiwa-Shi, Chiba, 277-8577, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, 811-1395, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Nagasaki University Hospital

Nagasaki, Nagasaki, 852-8501, Japan

Location

Osaka city University Hospital

Osaka, Osaka, 545-8586, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Koto-Ku, Tokyo, 135-8550, Japan

Location

Kyorin University Hospital

Mitaka-shi, Tokyo, 181-8611, Japan

Location

Centro de Estudios y Prevencion del Cancer (CEPREC)

Tuxtla Gutiérrez, Chiapas, 29038, Mexico

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, MX, 14080, Mexico

Location

Hospital Universitario Jose Eleuterio Gonzalez

Monterrey, Nuevo León, 64460, Mexico

Location

Radboud University Medical Center

Nijmegen, GA, 6525, Netherlands

Location

Instituto Nacional de Enfermedades Neoplasicas (INEN)

Surquillo, Lima region, 15038, Peru

Location

Hospital Daniel Alcides Carrion

Bellavista, Provincia Constitucional del Callao, 07016, Peru

Location

Hospital Goyeneche

Arequipa, 04001, Peru

Location

Hospital Nacional Arzobispo Loayza

Lima, 15082, Peru

Location

Centrum Medyczne HCP Sp. z o.o.

Poznan, Greater Poland Voivodeship, 61-485, Poland

Location

Szpital Kliniczny Przemienienia Pańskiego UM im. Karola Marcinkowskiego w Poznaniu

Poznan, Woj. Wielkopolskie, 60-569, Poland

Location

Fundacao Champalimaud

Lisbon, 1400-038, Portugal

Location

CUF Porto Hospital

Porto, 4100-180, Portugal

Location

Instituto Portugues de Oncologia do Porto

Porto, 4200-072, Portugal

Location

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

Location

Seoul National University Hospital

Jungni I Gu, Seoul, 3080, South Korea

Location

Asan Medical Center

Seoul, Seoul, 5505, South Korea

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

CHA Bundang Medical Center

Seongnam, 13496, South Korea

Location

Yonsei University Health System - Severance Hospital

Seoul, 3722, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Onkologikoa

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

Location

Hospital Universitario Virgen de la Arrixaca HUVA

El Palmar, Murcia, 30120, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Clinica Universidad de Navarra

Madrid, 28022, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28043, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

Kaohsiung City, 83301, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital NCKUH

Tainan, 704, Taiwan

Location

Chi Mei Medical Center CMMC - Yongkang branch

Tainan, 710, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Khon Kaen University KKU - Faculty of Medicine-Srinagarind Hospital

Khon Kaen, Muang, 40002, Thailand

Location

Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy

Bangkok, 10210, Thailand

Location

Rajavithi hospital

Bangkok, 10400, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University

Chiang Mai, 50200, Thailand

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, BS2 8ED, United Kingdom

Location

University College London Hospital NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Interventions

futibatinib; Cisplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The data for the outcome measures related to PFS, OS, ORR, DCR, and PFS per Investigator assessment was not collected or analyzed as planned because the study was terminated early due to poor recruitment.

Results Point of Contact

• Title: Taiho
• Organization: Taiho Oncology, Inc

clinicaltrialinfo@taihooncology.com

609-250-7336

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: September 18, 2019
• Study Start: January 6, 2021
• Primary Completion: April 22, 2024
• Study Completion: April 22, 2024
• Last Updated: February 7, 2025
• Results First Posted: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); ES (8); US (8); BE (4); BR (9); JP (12); GB (3); AR (2); TH (5); PT (3); DE (3); ME (3); HK (2); FR (8); NL (1); PE (4); IT (9); PL (2); TW (6); KR (8)