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

NCT ID: NCT04093362

Last Updated: 2025-02-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-06
• Study Completion Date: 2024-04-22

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

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 participants with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements. Eligible participants will be randomized on a 1:1 basis to the following study arms:

• Experimental Arm: Participants 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, participants will receive:

• Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (IV) infusion over 1 hour, followed by 500 millilliteres (mL) 0.9 percent (%) saline over 30 minutes; and
• Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by IV infusion over 30 minutes, beginning after completion of the cisplatin and saline infusions.

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

Participants 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. Participants 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.

Conditions

Advanced Cholangiocarcinoma; FGFR2 Gene Rearrangements

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Futibatinib

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.

Group Type: EXPERIMENTAL

Futibatinib

Intervention Type: DRUG

Oral tablets

Cisplatin/Gemcitabine

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.

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

IV infusion

Gemcitabine

Intervention Type: DRUG

IV infusion

Interventions

Futibatinib

Oral tablets

Intervention Type: DRUG

Cisplatin

IV infusion

Intervention Type: DRUG

Gemcitabine

IV infusion

Intervention Type: DRUG

Other Intervention Names

TAS-120

Eligibility Criteria

Inclusion Criteria

1. Provide written informed consent.

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

3. 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.

4. Participant has radiographically measurable disease per RECIST 1.1.

5. 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.

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 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

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 participants 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 participant will be excluded from this study if any of the following criteria are met:

1. Participant has received previous systemic anticancer therapy.

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

2. Participant 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 milliseconds (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.
• Participants 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 participant inappropriate for entry into this study.

8. Participants 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 participant is unable to take oral medication.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope National Medical Center

Duarte, California, United States

Norton Cancer Institute Audubon Hospital Campus Medical Plaza

Louisville, Kentucky, United States

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Medical Oncology Associates, PS - Summit Cancer Centers

Spokane, Washington, United States

Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, United States

Fundacion Favaloro para la Docencia e Investigacion Medica

Buenos Aires, Buenos Aires F.D., Argentina

Hospital de Gastroenterologia Dr. C. Bonorino Udaondo

Buenos Aires, Buenos Aires F.D., Argentina

Newcastle Private Hospital

Newcastle, New South Wales, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

UZ Antwerpen

Edegem, Antwerpen, Belgium

Algemeen Ziekenhuis AZ Sint-Maarten

Mechelen, Antwerpen, Belgium

AZ Delta Roeselare

Roeselare, Flanders, Belgium

CHC MontLégia

Liège, Liege, Belgium

IOP - Instituto de Oncologia do Parana

Curitiba, Paraná, Brazil

Instituto Nacional de Cancer Jose Alencar Gomes da Silva - INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Instituto Americas

Rio de Janeiro, Rio de Janeiro, Brazil

Cepho-Fm Abc

Santo André, São Paulo, Brazil

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, Brazil

Fundacao Antonio Prudente - A.C.Camargo Cancer Center

São Paulo, São Paulo, Brazil

Hospital Municipal Vila Santa Catarina

São Paulo, São Paulo, Brazil

Hospital Santa Marcelina HSM

São Paulo, São Paulo, Brazil

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, , France

Charite - Universitaetsmedizin Berlin

Berlin, , Germany

Universitaetsmedizin Mainz

Mainz, , Germany

Technische Universitaet Muenchen - Klinikum rechts der Isar

München, , Germany

The University of Hong Kong, Queen Mary Hospital

Hong Kong, , Hong Kong

The Chinese University of Hong Kong Prince of Wales Hospital

Shatin, , Hong Kong

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, , Italy

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Chiba University Hospital

Chiba, Chiba, Japan

National Cancer Center Hospital East

Kashiwa-Shi, Chiba, Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, Japan

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Nagasaki University Hospital

Nagasaki, Nagasaki, Japan

Osaka city University Hospital

Osaka, Osaka, Japan

Osaka University Hospital

Suita-shi, Osaka, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital of JFCR

Koto-Ku, Tokyo, Japan

Kyorin University Hospital

Mitaka-shi, Tokyo, Japan

Centro de Estudios y Prevencion del Cancer (CEPREC)

Tuxtla Gutiérrez, Chiapas, Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, MX, Mexico

Hospital Universitario Jose Eleuterio Gonzalez

Monterrey, Nuevo León, Mexico

Radboud University Medical Center

Nijmegen, GA, Netherlands

Instituto Nacional de Enfermedades Neoplasicas (INEN)

Surquillo, Lima region, Peru

Hospital Daniel Alcides Carrion

Bellavista, Provincia Constitucional del Callao, Peru

Hospital Goyeneche

Arequipa, , Peru

Hospital Nacional Arzobispo Loayza

Lima, , Peru

Centrum Medyczne HCP Sp. z o.o.

Poznan, Greater Poland Voivodeship, Poland

Szpital Kliniczny Przemienienia Pańskiego UM im. Karola Marcinkowskiego w Poznaniu

Poznan, Woj. Wielkopolskie, Poland

Fundacao Champalimaud

Lisbon, , Portugal

CUF Porto Hospital

Porto, , Portugal

Instituto Portugues de Oncologia do Porto

Porto, , Portugal

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Seoul National University Hospital

Jungni I Gu, Seoul, South Korea

Asan Medical Center

Seoul, Seoul, South Korea

Dong-A University Hospital

Busan, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

CHA Bundang Medical Center

Seongnam, , South Korea

Yonsei University Health System - Severance Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Onkologikoa

Donostia / San Sebastian, Gipuzkoa, Spain

Hospital Universitario Virgen de la Arrixaca HUVA

El Palmar, Murcia, Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Clinica Universidad de Navarra

Madrid, , Spain

MD Anderson Cancer Center

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital, Linkou

Taichung, , Taiwan

National Cheng Kung University Hospital NCKUH

Tainan City, , Taiwan

Chi Mei Medical Center CMMC - Yongkang branch

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University

Hat Yai, Changwat Songkhla, Thailand

Khon Kaen University KKU - Faculty of Medicine-Srinagarind Hospital

Khon Kaen, Muang, 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

Chiang Mai, , Thailand

University Hospitals Bristol NHS Foundation Trust

Bristol, , United Kingdom

University College London Hospital NHS Foundation Trust

London, , United Kingdom

Royal Free London NHS Foundation Trust

London, , United Kingdom

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-004630-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TAS-120-301

Identifier Type: -

Identifier Source: org_study_id