Clinical trial NCT05948475: Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma
Official title: A Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib VS Physician's Choice in Subjects With FGFR-altered, Chemotherapy- and FGFR Inhibitor-Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cholangiocarcinoma
Keywords: Refractory/Relapsed Cholangiocarcinoma
Lead sponsor: TransThera Sciences (Nanjing), Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-17
Enrollment: 200
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 study is a Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib versus Physician's Choice in Subjects with Fibroblast Growth Factor Receptor (FGFR)-altered, Chemotherapy- and FGFR Inhibitor-Refractory/Relapsed Cholangiocarcinoma

Detailed description: Approximately 200 subjects will be enrolled. Eligible subjects will be randomized in a 2:2:1 ratio to receive tinengotinib 8 mg QD, tinengotinib 10 mg QD or Physician's Choice in Part A; and eligible subjects will be randomized in a 2:1 ratio to receive the recommended Part B dose or selected dose or Physician's Choice in Part B.

Eligibility criteria: Inclusion Criteria:

1. ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Histologically or cytologically confirmed CCA/adenocarcinoma of biliary origin with radiological evidence of unresectable or metastatic disease.
3. Documentation of FGFR2 fusion/rearrangement gene status
4. Subjects must have received at least one line of prior chemotherapy and exactly one FDA approved FGFR inhibitor.

Exclusion Criteria:

1. Prior receipt of two or more FGFR inhibitors, either approved or investigational drugs.
2. Subjects with known brain or central nervous system (CNS) metastases that have radiologically or clinically progressed in the 28 days prior to initiation of therapy. Subjects with asymptomatic brain/CNS metastases or treated brain/CNS metastases that have been clinically stable for 14 days on steroids without escalation of steroids are eligible for enrollment.
3. Subjects with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, including those that have previously undergone potentially curative therapy.
4. Subjects who have received prior systemic therapy or investigational study drug ≤ 5 half-lives or 14 days, whichever is shorter, prior to starting the study drug or who have not recovered (grade ≤ 1 or at pretreatment baseline except tolerable grade 2 alopecia, fatigue/asthenia, and neuropathy due to trauma) from adverse events (AEs) of prior therapy.
5. Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval.
6. Subjects who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting the study drug or who have not recovered from AEs of prior therapy.
7. Subjects with uncontrolled hypertension (defined as blood pressure of ≥ 150 mm Hg systolic and/or ≥ 90 mm Hg diastolic despite adequate treatment with antihypertensive medications at screening)

Primary outcomes:
measure: Part A: Incidence, duration, and severity of adverse events (AEs)
timeFrame: Up to 30 days from study discontinuation
measure: Part B: PFS by BICR
timeFrame: From first study drug administration until the date of first documented progression assessed by BICR or date of death from any cause, whichever came first, assessed up to 24 months
Secondary outcomes:
measure: Part A: ORR by Investigator
timeFrame: Through study completion, an average of 9 months.
measure: Part A: DOR by Investigator
timeFrame: Through study completion, an average of 9 months.
measure: Part B:Overall Survival (OS)
timeFrame: From first study drug administration until the date of death from any cause, assessed up to 24 months.
measure: Part B: Objective Response Rate (ORR) by BICR and by Investigator:
timeFrame: Through study completion, an average of 9 months.
measure: Part B: Duration of Response (DOR) by BICR and by Investigator
timeFrame: Through study completion, an average of 9 months.
measure: Part B: PFS by Investigators per RECIST v1.1.
timeFrame: From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Hospitals
state: Illinois
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota- Masonic Cancer Center, M Health Fairview
state: Minnesota
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Asheville
country: United States
facility: Messino Cancer Centers
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology- Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH
city: Wiener Neustadt
country: Austria
facility: Landesklinikum Wiener Neustadt
city: Antwerp
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Avignon
country: France
facility: Institut Sainte Catherine - Institut du Cancer Avignon Provence
city: Besancon
country: France
facility: Centre Hospitalier Régional Universitaire de Besançon
city: Clichy
country: France
facility: Hopital Beaujon
city: Levallois-Perret
country: France
facility: Hopital Franco-Britannique - Fondation Cognacq-Jay
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire de Montpellier
city: Paris
country: France
facility: Hopital Saint Antoine
city: Villejuif
country: France
facility: Institut de Cancerologie Gustave Roussy
city: Baden
country: Germany
facility: Krebszentrum Reutlingen
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest gGmbH
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT)
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München Kum
city: Ancona
country: Italy
facility: Clinica Oncologica, Ospedali Riuniti Umberto 1
city: Candiolo
country: Italy
facility: Candiolo Cancer Institute - FPO IRCCS
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguard
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia IRCCS
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Luigi Vanvitelli
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
city: Parma
country: Italy
facility: Azienda Ospedaliera Universitaria di Parma
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Verona
country: Italy
facility: AOUI Verona - Ospedale Borgo Roma
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Gyeonggi-do
city: Jinju-si
country: Korea, Republic of
facility: Gyeongsang National University Hospital
state: Gyeongsangnam-do
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
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: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System - Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
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 Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofa
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: HM Hospital Universitario Madrid Sanchinarro - CIOCC
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital NHS
city: London
country: United Kingdom
facility: UCG-1st floor central
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust - Christie Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Milind Javle, MD
role: PRINCIPAL_INVESTIGATOR
References: