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

Overview

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.

Interventions

• Drug TAS-120
  TAS-120 is an oral FGFR inhibitor

Primary outcome measures

• ORR by independent central review [Time frame: 12 months after the study completion]

Secondary outcome measures (9)

• DoR by independent review [Time frame: up to 12 months after the study completion]
• PFS by independent review [Time frame: up to 12 months after the study completion]
• ORR per Investigator assessment [Time frame: up to 12 months after the study completion]
• DoR per Investigator assessment [Time frame: up to 12 months after the study completion]
• PFS per Investigator assessment [Time frame: up to 12 months after the study completion]
• OS [Time frame: up to 12 months after the study completion]
• Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 [Time frame: up to 12 months after the study completion]
• Change from Baseline in Quality of life as assessed by EORTC QLQ-C30 [Time frame: up to 12 months after the study completion]
• Change from Baseline in Quality of life as assessed by EuroQol-5D (EQ-5D ) [Time frame: up to 12 months after the study completion]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed, locally advanced, metastatic, or unresectable intrahepatic of extrahepatic Cholangiocarcinoma.
• Documented evidence of FGFR2 gene fusions or other FGFR2 rearrangement
• Received at least one prior systemic gemcitabine and platinum-based regimen for CCA
• Documentation of radiographic disease progression on the most recent prior therapy
• Measurable disease
• performance status 0 or 1
• Adequate organ function

Exclusion criteria

• History or current evidence of calcium and phosphate homeostasis disorder
• Current evidence of clinically significant retinal disorder
• Treatment with any of the following within the specified time frame prior to the first dose of futibatinib:

• 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
• Patients with locoregional therapy, eg, transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks
• 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
• 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.
• Patients with prior FGFR-directed therapy
• A serious illness or medical condition(s) including (but not limited to) the following:

• Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for ≥1 month
• Known acute systemic infection
• 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
• Significant gastrointestinal disorder(s) that could interfere with the absorption of futibatinib.
• 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.
• 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.
• Pregnant or lactating female.
• Known hypersensitivity or severe reaction to futibatinib or its excipients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• University of California San Diego UCSD - Moores Cancer Center — La Jolla
• Tampa General Hospital Cancer Institute — Tampa
• Henry Ford Health System — Detroit
• Gabrail Cancer Center Research — Canton
• Texas Oncology — Abilene
• The Liver Institute at Methodist Dallas Medical Center — Dallas
• Texas Oncology Methodist DFW — Dallas
• Texas Onc Methodist (Charlton) — Dallas
• … and 2 more centers

China · 10 centers

• Guangdong Provincial People's Hospitall — Guangzhou
• Harbin Medical University - Cancer Hospital — Harbin
• Jiangsu Provance Hospital — Nanjing
• Jilin Cancer Hospital — Changchun
• Shandong University - Shandong Cancer Hospital — Jinan
• Zhongahan Hospital Fudan unversity — Shanghai
• West China Hospital- Sichuan University — Chengdu
• Sir Run Run Shaw Hospital, Zhejiang University — Hangzhou
• … and 2 more centers

South Korea · 7 centers

• Inje University Haeundae Paik Hospital — Busan
• Dong-A University Hospital — Busan
• Kyungpook National University Hospital — Daegu
• Gyeongsang National University Hospital — Jinju
• CHA Bundang Medical Center — Seongnam
• Yonsei University Health System - Severance Hospital — Seoul
• The Catholic University of Korea, St. Mary's Hospital — Seoul

Spain · 7 centers

• Hospital Vall d'Hebron — Barcelona
• Institut Català d'Oncologia de l'Hospitalet de Llobregat - Hospital Duran i Reynals — Barcelona
• Hospital General Universitario Gregorio Maranon — Madrid
• Clinica Universidad de Navarra, Medical Oncology Service (Mariano Ponz Sarvise) — Madrid
• Hospital Universitario Fundación Jimenez Díaz — Madrid
• Hospital Universitario 12 de octubre — Madrid
• Clinica Universidad de Navarra — Pamplona

Brazil · 5 centers

• Instituto do Cancer do Estado de Sao Paulo — Cerqueira César
• IOP - Instituto de Oncologia do Parana — Curitiba
• Hospital Erasto Gaertner — Curitiba
• Hospital de Base de Sao Jose do Rio Preto — São José do Rio Preto
• Fundacao Antonio Prudente - A.C.Camargo Cancer Center — São Paulo

Japan · 5 centers

• Tohoku University Hospital — Sendai
• National Cancer Center Hospital East — Kashiwa-Shi
• Nagasaki University Hospital — Nagasaki
• Nagoya University Hospital — Nagoya
• Osaka Metropolitan University Hospital — Osaka-Fu

Canada · 4 centers

• Sunnybrook Health Sciences Center — Toronto
• Grand River Hospital - Grand River Regional Cancer Centre (GRRCC) — Kitchener
• University of Toronto — Toronto
• McGill University Health Center — Montreal

Poland · 4 centers

• Szpital Wojewdzki w Koszalinie im. Mikoaja Kopernika — Koszalin
• Centrum Onkologii Ziemi Lubelskiej im. w. Jana z Dukli — Lublin
• Europejskie Centrum Zdrowia Otwock Sp. Z.o.o. — Otwock
• Centrum Onkologii-Instytut im. Marii Skłodowskiej - Curie — Warsaw

Argentina · 3 centers

• Hospital Britanico — Buenos Aires
• CEMIC — CABA
• Sanatorio de la Mujer — Rosario

Australia · 3 centers

• St Vincent's Hospital Sydney - The Kinghorn Cancer Centre — Sydney
• Alfred Health, Medical Oncology Unit, Second floor William Buckland Radiotherapy Center — Melbourne
• St John of God Subiaco Hospital — Subiaco

Italy · 3 centers

• Policlinico S. Orsola-Malpighi — Bologna
• IRCCS Humanitas Research Hospital — Rozzano
• AOUI Verona - Ospedale Borgo Roma — Verona

Hong Kong · 2 centers

• The University of Hong Kong — Hong Kong Island
• The Chinese University of Hong Kong Prince of Wales Hospital — New Territories

Portugal · 2 centers

• Fundação Champalimaud — Lisbon
• Centro Hospitalar Lisboa Norte CHLN EPE - Hospital de Santa Maria — Lisbon

Identifiers

NCT: NCT05727176 · TAS-120-205 · 2023-503665-39 · 2022-9400

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗