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Study of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement

Phase 2
Recruiting
Conditions
Advanced Cholangiocarcinoma
FGFR2 Fusions
Gene Rearrangement
Interventions
Registration Number
NCT05727176
Lead Sponsor
Taiho Oncology, Inc.
Brief Summary

This is an open-label, multinational, randomized Phase 2 study confirming the clinical benefit of 20 mg futibatinib and evaluating the safety and efficacy of 16 mg futibatinib in previously treated CCA harboring FGFR2 gene fusions and other rearrangements.

Detailed Description

This is an open-label, multinational, randomized Phase 2 study confirming the clinical benefit of 20 mg futibatinib and evaluating the safety and efficacy of 16 mg futibatinib in previously treated CCA harboring FGFR2 gene fusions and other rearrangements. Eligible patients will be randomized on a 1:1 basis to the following study arms:

* Patients will receive futibatinib at an oral dose of 16 mg, administered daily (QD) on every day of a 21-day cycle.

* Patients will receive futibatinib at an oral dose of 20 mg, administered daily (QD) on every day of a 21-day cycle.

Patients 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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
Inclusion Criteria
  1. Histologically or cytologically confirmed, locally advanced, metastatic, or unresectable intrahepatic of extrahepatic Cholangiocarcinoma.
  2. Documented evidence of FGFR2 gene fusions or other FGFR2 rearrangement
  3. Received at least one prior systemic gemcitabine and platinum-based regimen for CCA
  4. Documentation of radiographic disease progression on the most recent prior therapy
  5. Measurable disease
  6. performance status 0 or 1
  7. Adequate organ function
Exclusion Criteria
  1. History or current evidence of calcium and phosphate homeostasis disorder

  2. Current evidence of clinically significant retinal disorder

  3. Treatment with any of the following within the specified time frame prior to the first dose of futibatinib:

    1. Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of futibatinib) and radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks
    2. Patients with locoregional therapy, eg, transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks
    3. Any non investigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to futibatinib. Endocrine therapy is allowed for patients with breast or prostate cancer
    4. Targeted therapy or immunotherapy within 3 weeks or within 5 half lives Any investigational agent received within 5 half-lives of the drug or 4 weeks, whichever is shorter.
    5. Patients with prior FGFR-directed therapy
  4. A serious illness or medical condition(s) including (but not limited to) the following:

    1. Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for ≥1 month
    2. Known acute systemic infection
    3. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV New York Heart Association [NYHA] Classification) within the previous 2 months; if >2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms
    4. Significant gastrointestinal disorder(s) that could interfere with the absorption of futibatinib.
    5. 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.
  5. Known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen. Exceptions must be discussed with the Sponsor prior to patient enrollment.

  6. Pregnant or lactating female.

  7. Known hypersensitivity or severe reaction to futibatinib or its excipients.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment Arm ATAS-120TAS-120 (20mg) tablets, oral; 21-day cycle
Treatment Arm BTAS-120TAS-120 (16mg) tablets, oral; 21-day cycle
Primary Outcome Measures
NameTimeMethod
ORR by independent central review12 months after the study completion

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

Secondary Outcome Measures
NameTimeMethod
Change from Baseline in Quality of life as assessed by EORTC QLQ-C30up to 12 months after the study completion

Change from Baseline in quality of life as assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score

PFS per Investigator assessmentup to 12 months after the study completion

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

DoR by independent reviewup to 12 months after the study completion

defined as time from the first documentation of response to the first documentation of objective tumor progression by ICR (per RECIST 1.1) or death due to any cause, whichever occurs first

Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0up to 12 months after the study completion

Safety will be assessed based on reported AEs (including SAEs), graded by CTCAE V5.0. including serious adverse events (SAEs) and dose modifications.

PFS by independent reviewup to 12 months after the study completion

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

ORR per Investigator assessmentup to 12 months after the study completion

defined as proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST v1.1).

OSup to 12 months after the study completion

defined as the time from the date of randomization until the date of death due to any cause.

DoR per Investigator assessmentup to 12 months after the study completion

defined as time from the first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first

Change from Baseline in Quality of life as assessed by EuroQol-5D (EQ-5D )up to 12 months after the study completion

Change from Baseline in Quality of Life as Assessed by European Quality of Life - 5 Dimensions-3 Levels (EQ-5D-3L) Scale Score.

Trial Locations

Locations (57)

Hospital Universitario 12 de octubre

🇪🇸

Madrid, Spain

Clinica Universidad de Navarra

🇪🇸

Pamplona, Spain

St John of God Subiaco Hospital

🇦🇺

Subiaco, Western Australia, Australia

Instituto do Cancer do Estado de Sao Paulo

🇧🇷

Cerqueira César, Brazil

IOP - Instituto de Oncologia do Parana

🇧🇷

Curitiba, Brazil

Hospital Erasto Gaertner

🇧🇷

Curitiba, Brazil

Hospital de Base de Sao Jose do Rio Preto

🇧🇷

São José Do Rio Preto, Brazil

Nagoya University Hospital

🇯🇵

Nagoya-shi, Japan

Osaka Metropolitan University Hospital

🇯🇵

Osaka-Fu, Japan

Inje University Haeundae Paik Hospital

🇰🇷

Busan, Korea, Republic of

Dong-A University Hospital

🇰🇷

Busan, Korea, Republic of

Kyungpook National University Hospital

🇰🇷

Daegu, Korea, Republic of

Gyeongsang National University Hospital

🇰🇷

Jinju, Korea, Republic of

CHA Bundang Medical Center

🇰🇷

Seongnam, Korea, Republic of

Yonsei University Health System - Severance Hospital

🇰🇷

Seoul, Korea, Republic of

The Catholic University of Korea, St. Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

Szpital Wojewdzki w Koszalinie im. Mikoaja Kopernika

🇵🇱

Koszalin, Poland

Centrum Onkologii Ziemi Lubelskiej im. w. Jana z Dukli

🇵🇱

Lublin, Poland

Europejskie Centrum Zdrowia Otwock Sp. Z.o.o.

🇵🇱

Otwock, Poland

Centrum Onkologii-Instytut im. Marii Skłodowskiej - Curie

🇵🇱

Warszawa, Poland

Fundação Champalimaud

🇵🇹

Lisboa, Portugal

Centro Hospitalar Lisboa Norte CHLN EPE - Hospital de Santa Maria

🇵🇹

Lisbon, Portugal

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Institut Català d'Oncologia de l'Hospitalet de Llobregat - Hospital Duran i Reynals

🇪🇸

Barcelona, Spain

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

Clinica Universidad de Navarra, Medical Oncology Service (Mariano Ponz Sarvise)

🇪🇸

Madrid, Spain

Hospital Universitario Fundación Jimenez Díaz

🇪🇸

Madrid, Spain

University of California San Diego UCSD - Moores Cancer Center

🇺🇸

La Jolla, California, United States

Tampa General Hospital Cancer Institute

🇺🇸

Tampa, Florida, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Gabrail Cancer Center Research

🇺🇸

Canton, Ohio, United States

Texas Oncology

🇺🇸

Abilene, Texas, United States

The Liver Institute at Methodist Dallas Medical Center

🇺🇸

Dallas, Texas, United States

Texas Onc Methodist (Charlton)

🇺🇸

Dallas, Texas, United States

Center for Oncology and Blood Disorders

🇺🇸

Houston, Texas, United States

CEMIC

🇦🇷

Caba, Argentina

Hospital Britanico

🇦🇷

Ciudad Autonoma de Buenos Aires, Argentina

Sanatorio de la Mujer

🇦🇷

Rosario, Argentina

St Vincent's Hospital Sydney - The Kinghorn Cancer Centre

🇦🇺

Sydney, New South Wales, Australia

Alfred Health, Medical Oncology Unit, Second floor William Buckland Radiotherapy Center

🇦🇺

Melbourne, Victoria, Australia

Fundacao Antonio Prudente - A.C.Camargo Cancer Center

🇧🇷

São Paulo, Brazil

Guangdong Provincial People's Hospitall

🇨🇳

Guangzhou, Guangdong, China

Harbin Medical University - Cancer Hospital

🇨🇳

Harbin, Heilongjiang, China

Jilin Cancer Hospital

🇨🇳

Changchun, Jilin, China

Shandong University - Shandong Cancer Hospital

🇨🇳

Jinan, Shandong, China

West China Hospital- Sichuan University

🇨🇳

Chengdu, Sichuan, China

Sir Run Run Shaw Hospital, Zhejiang University

🇨🇳

Hangzhou, Zhejiang, China

Shanghai Gobroad Cancer Hospital China Pharmaceutical University

🇨🇳

Shanghai, China

Tongji University Shanghai East Hospital

🇨🇳

Shanghai, China

The University of Hong Kong

🇭🇰

Hong Kong Island, Hong Kong

The Chinese University of Hong Kong Prince of Wales Hospital

🇭🇰

New Territories, Hong Kong

Policlinico S. Orsola-Malpighi

🇮🇹

Bologna, Italy

IRCCS Humanitas Research Hospital

🇮🇹

Rozzano, Italy

AOUI Verona - Ospedale Borgo Roma

🇮🇹

Verona, Italy

Tohoku University Hospital

🇯🇵

Sendai, Miyagi, Japan

National Cancer Center Hospital East

🇯🇵

Kashiwa-Shi, Japan

Nagasaki University Hospital

🇯🇵

Nagasaki-shi, Japan

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