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Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma

Phase 3
Recruiting
Conditions
Cholangiocarcinoma
Interventions
Registration Number
NCT05948475
Lead Sponsor
TransThera Sciences (Nanjing), Inc.
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Tinengotinib 10 mg QDTinengotinib 10 mgTinengotinib will be administered in 28-day cycles.
Physician's ChoicePhysician's ChoicePhysician's Choice treatments include FOLFOX or FOLFIRI
Tinengotinib 8 mg QDTinengotinib 8 mgTinengotinib will be administered in 28-day cycles.
Primary Outcome Measures
NameTimeMethod
Part A: Incidence, duration, and severity of adverse events (AEs)Up to 30 days from study discontinuation

As assessed per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (or the most current version).

Part B: PFS by BICRFrom 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

Progression-free survival (PFS) by BICR: PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or date of death due to any cause, whichever is earlier.

Secondary Outcome Measures
NameTimeMethod
Part B: Objective Response Rate (ORR) by BICR and by Investigator:Through study completion, an average of 9 months.

The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.

Part B: Duration of Response (DOR) by BICR and by InvestigatorThrough study completion, an average of 9 months.

Duration of response for CR or PR based on RECIST version 1.1.

Part A: ORR by InvestigatorThrough study completion, an average of 9 months.

ORR:objective response rate (ORR), the proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.

Part B:Overall Survival (OS)From first study drug administration until the date of death from any cause, assessed up to 24 months.

OS is defined as the time from date of randomization to date of death of any cause.

Part B: PFS by Investigators per RECIST v1.1.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.

PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Part A: DOR by InvestigatorThrough study completion, an average of 9 months.

Duration of response for CR or PR based on RECIST version 1.1.

Trial Locations

Locations (86)

UCLA Medical Center

🇺🇸

Santa Monica, California, United States

The University of Chicago Hospitals

🇺🇸

Chicago, Illinois, United States

UMass Memorial Medical Center

🇺🇸

Worcester, Massachusetts, United States

The University of Kansas Cancer Center

🇺🇸

Westwood, California, United States

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

Hopital Franco-Britannique - Fondation Cognacq-Jay

🇫🇷

Levallois-Perret, France

Asklepios Klinik Altona

🇩🇪

Hamburg, Germany

Ludwig-Maximilians-Universität München Kum

🇩🇪

München, Germany

Chonnam National University Hwasun Hospital

🇰🇷

Hwasun, Jeollanam-do, Korea, Republic of

Yonsei University Health System - Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Hospital Universitari Vall d´Hebron

🇪🇸

Barcelona, Spain

Hospital Clínic de Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario Fundacion Jimenez Diaz

🇪🇸

Madrid, Spain

Hospital Clinico Universitario de Santiago de Compostela

🇪🇸

Santiago De Compostela, Spain

Azienda Ospedaliero-Universitaria Pisana

🇮🇹

Pisa, Italy

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

🇮🇹

Siena, Italy

Roswell Park Comprehensive Cancer Center

🇺🇸

Buffalo, New York, United States

Messino Cancer Centers

🇺🇸

Asheville, North Carolina, United States

Texas Oncology-Sammons Cancer Center

🇺🇸

Dallas, Texas, United States

University of Virginia Cancer Center

🇺🇸

Charlottesville, Virginia, United States

Universitair Ziekenhuis Antwerpen

🇧🇪

Antwerp, Belgium

Landesklinikum Wiener Neustadt

🇦🇹

Wiener Neustadt, Austria

Institut Sainte Catherine - Institut du Cancer Avignon Provence

🇫🇷

Avignon, France

Universitair Ziekenhuis Leuven

🇧🇪

Leuven, Belgium

Centre Hospitalier Régional Universitaire de Besançon

🇫🇷

Besancon, France

Hopital Beaujon

🇫🇷

Clichy, France

Centre Hospitalier Universitaire de Montpellier

🇫🇷

Montpellier, France

Clinique de la Sauvegarde

🇫🇷

Lyon, France

Hopital Saint Antoine

🇫🇷

Paris, France

Institut de Cancerologie Gustave Roussy

🇫🇷

Villejuif, France

Krebszentrum Reutlingen

🇩🇪

Baden, Germany

Krankenhaus Nordwest gGmbH

🇩🇪

Frankfurt, Germany

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT)

🇩🇪

Heidelberg, Germany

Clinica Oncologica, Ospedali Riuniti Umberto 1

🇮🇹

Ancona, Italy

Candiolo Cancer Institute - FPO IRCCS

🇮🇹

Candiolo, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

🇮🇹

Milano, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

🇮🇹

Meldola, Italy

ASST Grande Ospedale Metropolitano Niguard

🇮🇹

Milano, Italy

Istituto Europeo di Oncologia IRCCS

🇮🇹

Milan, Italy

Azienda Ospedaliera Universitaria Luigi Vanvitelli

🇮🇹

Napoli, Italy

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

🇮🇹

Napoli, Italy

Azienda Ospedaliera Universitaria di Parma

🇮🇹

Parma, Italy

Humanitas Research Hospital

🇮🇹

Rozzano, Italy

AOUI Verona - Ospedale Borgo Roma

🇮🇹

Verona, Italy

CHA Bundang Medical Center

🇰🇷

Seongnam-si, Gyeonggi-do, Korea, Republic of

Gyeongsang National University Hospital

🇰🇷

Jinju-si, Gyeongsangnam-do, Korea, Republic of

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

Amsterdam UMC, location AMC

🇳🇱

Amsterdam, Netherlands

Korea University Guro Hospital

🇰🇷

Seoul, Korea, Republic of

Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie

🇵🇱

Warszawa, Poland

Centro Hospitalar Lisboa Norte CHLN EPE - Hospital de Santa Maria

🇵🇹

Lisbon, Portugal

Fundação Champalimaud

🇵🇹

Lisboa, Portugal

Clinica Universidad de Navarra

🇪🇸

Pamplona, Spain

Hospital Universitario Reina Sofa

🇪🇸

Cordoba, Spain

HM Hospital Universitario Madrid Sanchinarro - CIOCC

🇪🇸

Madrid, Spain

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

Hospital Universitario 12 de octubre

🇪🇸

Madrid, Spain

Hospital Universitario Ramón y Cajal

🇪🇸

Madrid, Spain

Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

🇨🇳

Kaohsiung, Taiwan

Hospital Universitario Miguel Servet

🇪🇸

Zaragoza, Spain

The Christie NHS Foundation Trust - Christie Hospital

🇬🇧

Manchester, United Kingdom

Royal Marsden Hospital NHS

🇬🇧

London, United Kingdom

UCG-1st floor central

🇬🇧

London, United Kingdom

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, United Kingdom

Stanford Cancer Center

🇺🇸

Stanford, California, United States

Mount Sinai Comprehensive Cancer Center

🇺🇸

Miami Beach, Florida, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Gachon University Gil Medical Center

🇰🇷

Incheon, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Ordensklinikum Linz GmbH

🇦🇹

Linz, Austria

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

🇨🇳

Kaohsiung, Taiwan

Taichung Veterans General Hospital

🇨🇳

Taichung, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Henry Ford

🇺🇸

Detroit, Michigan, United States

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

University of Minnesota- Masonic Cancer Center, M Health Fairview

🇺🇸

Minneapolis, Minnesota, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Tennessee Oncology- Nashville

🇺🇸

Nashville, Tennessee, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

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