Clinical trial NCT05727176: Study of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement
Official title: Phase 2 Study of Futibatinib 20 mg and 16 mg in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusions or Rearrangements
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Cholangiocarcinoma
FGFR2 Fusions
Gene Rearrangement
Keywords: Futibatinib
Advanced cholangiocarcinoma
cholangiocarcinoma
FGFR2
Fusion
Rearrangemen
TAS-120
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ORR by independent central review
timeFrame: 12 months after the study completion
Secondary outcomes:
measure: DoR by independent review
timeFrame: up to 12 months after the study completion
measure: PFS by independent review
timeFrame: up to 12 months after the study completion
measure: ORR per Investigator assessment
timeFrame: up to 12 months after the study completion
measure: DoR per Investigator assessment
timeFrame: up to 12 months after the study completion
measure: PFS per Investigator assessment
timeFrame: up to 12 months after the study completion
measure: OS
timeFrame: up to 12 months after the study completion
measure: Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0
timeFrame: up to 12 months after the study completion
measure: Change from Baseline in Quality of life as assessed by EORTC QLQ-C30
timeFrame: up to 12 months after the study completion
measure: Change from Baseline in Quality of life as assessed by EuroQol-5D (EQ-5D )
timeFrame: up to 12 months after the study completion
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego UCSD - Moores Cancer Center
state: California
city: Tampa
country: United States
facility: Tampa General Hospital Cancer Institute
state: Florida
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Abilene
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Methodist DFW
state: Texas
city: Dallas
country: United States
facility: Texas Onc Methodist (Charlton)
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Northeast
state: Texas
city: Houston
country: United States
facility: Center for Oncology and Blood Disorders
state: Texas
city: Caba
country: Argentina
facility: CEMIC
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Britanico
city: Rosario
country: Argentina
facility: Sanatorio de la Mujer
city: Sydney
country: Australia
facility: St Vincent's Hospital Sydney - The Kinghorn Cancer Centre
state: New South Wales
city: Melbourne
country: Australia
facility: Alfred Health, Medical Oncology Unit, Second floor William Buckland Radiotherapy Center
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Cerqueira César
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo
city: Curitiba
country: Brazil
facility: IOP - Instituto de Oncologia do Parana
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: São José Do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
city: São Paulo
country: Brazil
facility: Fundacao Antonio Prudente - A.C.Camargo Cancer Center
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospitall
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University - Cancer Hospital
state: Heilongjiang
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Jinan
country: China
facility: Shandong University - Shandong Cancer Hospital
state: Shandong
city: Chengdu
country: China
facility: West China Hospital- Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University
state: Zhejiang
city: Shanghai
country: China
facility: Shanghai Gobroad Cancer Hospital China Pharmaceutical University
city: Shanghai
country: China
facility: Tongji University Shanghai East Hospital
city: Hong Kong Island
country: Hong Kong
facility: The University of Hong Kong
city: New Territories
country: Hong Kong
facility: The Chinese University of Hong Kong Prince of Wales Hospital
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Rozzano
country: Italy
facility: IRCCS Humanitas Research Hospital
city: Verona
country: Italy
facility: AOUI Verona - Ospedale Borgo Roma
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Kashiwa-Shi
country: Japan
facility: National Cancer Center Hospital East
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
city: Osaka-Fu
country: Japan
facility: Osaka Metropolitan University Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System - Severance Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, St. Mary's Hospital
city: Koszalin
country: Poland
facility: Szpital Wojewdzki w Koszalinie im. Mikoaja Kopernika
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. w. Jana z Dukli
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Sp. Z.o.o.
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. Marii Skłodowskiej - Curie
city: Lisboa
country: Portugal
facility: Fundação Champalimaud
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisboa Norte CHLN EPE - Hospital de Santa Maria
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia de l'Hospitalet de Llobregat - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra, Medical Oncology Service (Mariano Ponz Sarvise)
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jimenez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de octubre
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
References: