Clinical trial NCT04093362: Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements
Official title: A Phase 3, Open-Label, Randomized Study of Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements FOENIX-CCA3
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Advanced Cholangiocarcinoma
FGFR2 Gene Rearrangements
Keywords: Futibatinib
Advanced Cholangiocarcinoma
FGFR2
Fusion
Rearrangement
TAS-120
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2019-09-18
Enrollment: 10
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, 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.

Eligibility criteria: Inclusion Criteria:

A participant must meet all of the following inclusion criteria to be eligible for enrollment in this study:

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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 28 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 28 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 28 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 28 months
measure: Progression-Free Survival (PFS) Per Investigator Assessment
timeFrame: Up to approximately 28 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 28 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute Audubon Hospital Campus Medical Plaza
state: Kentucky
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates, PS - Summit Cancer Centers
state: Washington
city: Madison
country: United States
facility: Carbone Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Fundacion Favaloro para la Docencia e Investigacion Medica
state: Caba
city: Buenos Aires
country: Argentina
facility: Hospital de Gastroenterologia Dr. C. Bonorino Udaondo
state: Caba
city: Newcastle
country: Australia
facility: Newcastle Private Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Mechelen
country: Belgium
facility: Algemeen Ziekenhuis AZ Sint-Maarten
state: Antwerpen
city: Roeselare
country: Belgium
facility: AZ Delta Roeselare
state: Flemish Region
city: Liège
country: Belgium
facility: CHC MontLégia
state: Liege
city: Curitiba
country: Brazil
facility: IOP - Instituto de Oncologia do Parana
state: PR
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Cancer Jose Alencar Gomes da Silva - INCA
state: RJ
city: Rio De Janeiro
country: Brazil
facility: Instituto Americas
state: RJ
city: Santo Andre
country: Brazil
facility: Cepho-Fm Abc
state: SP
city: São José Do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: SP
city: São Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo
state: SP
city: São Paulo
country: Brazil
facility: Fundacao Antonio Prudente - A.C.Camargo Cancer Center
state: SP
city: São Paulo
country: Brazil
facility: Hospital Municipal Vila Santa Catarina
state: SP
city: São Paulo
country: Brazil
facility: Hospital Santa Marcelina HSM
state: SP
city: Clichy
country: France
facility: Hopitaux Universitaires Paris Nord Val de Seine - Hopital Beaujon
city: Dijon
country: France
facility: Centre Georges-Francois Leclerc
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble
city: Lyon
country: France
facility: Centre Leon Berard
city: Montbéliard
country: France
facility: CHRU Besancon
city: Reims
country: France
facility: CHU Reims
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe ICAENS
city: Tours
country: France
facility: CHU de TOURS - Hopital Trousseau
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin
city: Mainz
country: Germany
facility: Universitaetsmedizin Mainz
city: Muenchen
country: Germany
facility: Technische Universitaet Muenchen - Klinikum rechts der Isar
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong, Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong Prince of Wales Hospital
city: Candiolo
country: Italy
facility: Candiolo Cancer Institute - FPO IRCCS
city: Lucca
country: Italy
facility: Ospedale Versilia
city: Monserrato
country: Italy
facility: AOU di Cagliari
city: Novara
country: Italy
facility: Ospedale Maggiore della Carita di Novara
city: Parma
country: Italy
facility: Servizio Sanitario Regionale Emilia-Romagna - Azienda Ospedaliero-Universitaria di Parma Ospedale Maggiore
city: Roma
country: Italy
facility: Policlinico Uni. Campus Bio-Medico
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Verona
country: Italy
facility: AOUI Verona - Ospedale Borgo Roma
city: Vicenza
country: Italy
facility: Azienda ULSS 8 Berica
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
state: Chiba
city: Kashiwa-Shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
state: Fukuoka
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Yokohama-Shi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
state: Nagasaki
city: Osaka-shi
country: Japan
facility: Osaka city University Hospital
state: Osaka
city: Suita-shi
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Mitaka-shi
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-Do
city: Jungni I Gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Seul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook 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: Samsung Medical Center
city: Tuxtla Gutiérrez
country: Mexico
facility: Centro de Estudios y Prevencion del Cancer (CEPREC)
state: Chiapas
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: MX
city: Monterrey
country: Mexico
facility: Hospital Universitario Jose Eleuterio Gonzalez
state: Nuevo Leon
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: GA
city: Bellavista
country: Peru
facility: Hospital Daniel Alcides Carrion
state: Callao
city: Surquillo
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas (INEN)
state: Lima
city: Arequipa
country: Peru
facility: Hospital Goyeneche
city: Lima
country: Peru
facility: Hospital Nacional Arzobispo Loayza
city: Poznań
country: Poland
facility: Centrum Medyczne HCP Sp. z o.o.
state: Wielkopolskie
city: Poznań
country: Poland
facility: Szpital Kliniczny Przemienienia Pańskiego UM im. Karola Marcinkowskiego w Poznaniu
state: Woj. Wielkopolskie
city: Lisboa
country: Portugal
facility: Fundacao Champalimaud
city: Porto
country: Portugal
facility: CUF Porto Hospital
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto
city: Donostia-San Sebastian
country: Spain
facility: Onkologikoa
state: Gipuzkoa
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca HUVA
state: Murcia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
city: Taichung
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital NCKUH
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center CMMC - Yongkang branch
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Khon Kaen
country: Thailand
facility: Khon Kaen University KKU - Faculty of Medicine-Srinagarind Hospital
state: Muang
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University
state: Songkhla
city: Bangkok
country: Thailand
facility: Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy
city: Bangkok
country: Thailand
facility: Rajavithi hospital
city: ChiangMai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
Study officials:
References: