Derazantinib in Subjects With FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma (FIDES-01)

November 29, 2023 updated by: Basilea Pharmaceutica

A Pivotal Study of Derazantinib in Patients With Inoperable or Advanced Intrahepatic Cholangiocarcinoma and FGFR2 Gene Fusions or FGFR2 Gene Mutations or Amplifications

This Phase II, open-label, single-arm study evaluated the anti-cancer activity of derazantinib in subjects with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) who received at least one prior regimen of systemic therapy. Patients received an oral once-daily total dose of 300 mg derazantinib capsules.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This was a multi-center, open-label, single arm study which evaluated the anti-cancer activity of derazantinib in adult patients with inoperable or advanced iCCA in the following study population:

Patients with inoperable or advanced iCCA and with fibroblast growth factor receptor 2 (FGFR2) fusions (Substudy 1) or FGFR2 mutations/amplifications (Substudy 2), treated with at least one prior regimen of systemic therapy.

Derazantinib was supplied as 100 mg capsules. A dose of 300 mg once-daily (three capsules of 100 mg each) of derazantinib was administered orally to patients, 1 hour before, or 2 hours after, a meal.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
148

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Available

Available

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
      • Brussels, Belgium, 1070
        • Hopital Erasme
      • Edegem, Belgium, 2650
        • Antwerp University Hospital
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
  • France
      • La Tronche, France, 38700
        • Chu Grenoble Alpes
      • Villejuif, France, 94805
        • Gustave Roussy
  • Germany
      • Frankfurt am Main, Germany, 60590
        • Universitatsklinikum Frankfurt
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf (UKE)
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover (MHH)
      • Homburg, Germany, 66421
        • Universitätsklinikum des Saarlandes
      • Mainz, Germany, 55131
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Ireland
      • Dublin, Ireland, D08 NHY1
        • St. James's Hospital
  • Italy
      • Bologna, Italy, 40138
        • Sant'Orsola-Malpighi Hospital, University of Bologna
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Monza, Italy, 20900
        • Ospedale San Gerardo
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto - IRCCS
      • Pisa, Italy, 56126
        • Azienda Ospedaliero-Universitaria Pisana
      • Rozzano, Italy, 20089
        • Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS
  • Korea, Republic of
      • Seoul, Korea, Republic of, 3080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 6351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 6591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Spain
      • Barcelona, Spain, 08035
        • Vall d'Hebron University Hospital
      • Barcelona, Spain, 08908
        • Catalan Institute of Oncology
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
  • Switzerland
      • Basel, Switzerland, 4031
        • Universitatsspital Basel
  • United Kingdom
      • Euston, United Kingdom, NW1 2BU
        • University College London Hospitals NHS Foundation Trust
      • Glasgow, United Kingdom, G120YN
        • Beatson West Of Scotland Cancer Centre
      • Sutton, United Kingdom, SM2 5PT
        • The Royal Marsden
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
      • Tampa, Florida, United States, 33612-9416
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory University
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10065-6800
        • Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center for Prostate and Urologic Cancers
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of The University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390
        • The University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. Signed written informed consent granted prior to initiation of any study-specific procedures
  2. 18 years of age or older
  3. Histologically or cytologically confirmed locally advanced, inoperable, or metastatic iCCA or mixed histology tumors

  4. Substudy 1:

    FGFR2 fusion status based on the following assessments:

    a) If central laboratory was designated by Sponsor: Positive FISH test; and/or b) If non-central laboratory: i) Positive FISH or NGS test: patients were potentially enrolled and started dosing, but central confirmation was required* ii) Negative FISH or NGS test: tissue was submitted to the central laboratory designated by the Sponsor, and patients were only enrolled in case the central test was positive

    *By used standard protocols and approved by local IRB/EC, by CLIA or other similar agency.

    Substudy 2:

    FGFR2 mutation/amplification status based on local NGS testing performed or commissioned by the respective study site.

  5. Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression
  6. Measurable disease by RECIST version 1.1 criteria
  7. ECOG performance status ≤ 1

  8. Adequate organ functions as indicated by the following laboratory values (based on screening visit values from the central laboratory).

    • Hematological

      • Hemoglobin (Hgb) ≥ 9.0 g/dL
      • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
      • Platelet count ≥ 75 x 109/L
      • International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤ 3 for subjects who received anticoagulant therapy such as Coumadin or heparin

    • Hepatic

      • Total bilirubin ≤ 2 x ULN
      • AST and ALT ≤ 3 ULN (≤ 5 x ULN for subjects with liver metastases)
      • Albumin ≥ 2.8 g/dL

    • Renal

      • Serum creatinine ≤ 1.5 x ULN
      • Creatinine clearance of ≥ 30 mL/min as estimated by the Cockcroft-Gault equation
  9. Female and male patients of child-producing potential must had agreed to avoid becoming pregnant or impregnating a partner, respectively, used double-barrier contraceptive measures, oral contraception, or had to avoid of intercourse, during the study, and until at least 120 for 90 days after the last dose of derazantinib.

Male or female patients of child-producing potential must had agreed to comply with one of the following until at least 120 days after the last dose of derazantinib:

  1. Abstinence from heterosexual activity
  2. Using (or having their partner use) an acceptable method of contraception during heterosexual activity.

Key Exclusion Criteria:

  1. Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:

    • One chemotherapy or biological (e.g., antibody) cycle interval
    • Five half-lives of any small-molecule investigational or licensed medicinal product
    • Two weeks, for any investigational medicinal product with an unknown half-life
    • Four weeks of curative radiotherapy
    • Seven days of palliative radiotherapy
    • 28 days of radiotherapy
  2. Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of derazantinib
  3. Previous treatment with any FGFR inhibitor (e.g., Balversa® [erdafitinib], Pemazyre® [pemigatinib], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib, dovitinib, nintedanib, AZD4547, LY2784455).
  4. Patients who were unable or unwilling to swallow the complete daily dose of derazantinib capsules
  5. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must had stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or had CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)
  6. Evidence of clinically significant corneal or retinal disorder which was likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination.
  7. Uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the subjects had to be treated and disorders/complications should had been resolved within 2 weeks prior to the first dose of derazantinib)

  8. History of significant cardiac disorders:

    • Myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of derazantinib (MI that occurred > 6 months prior to the first dose of derazantinib was permitted)
    • QTcF >450 msec (males or females)

  9. Serum electrolyte abnormalities defined as follows:

    • Hyperphosphataemia: Serum phosphate > institutional ULN
    • Hyperkalemia: > 6.0 mmol/L
    • Hypokalemia: < 3.0 mmol/L
    • Hypercalcemia: corrected serum calcium < 1.75 mmol/L (< 7.0 mg/dL)
    • Hypocalcemia: corrected serum calcium > 3.1 mmol/L (> 12.5 mg/dL)
    • Hypomagnesemia: < 0.4 mmol/L (< 0.9 mg/dL)
  10. Significant gastrointestinal disorder(s) that could had, in the opinion of the Investigator, interfered with the absorption, metabolism, or excretion of derazantinib (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
  11. History of additional malignancy that was progressing or required active treatment. Exceptions included basal cell carcinoma of the skin, squamous cell carcinoma of the skin that had undergone potentially curative therapy, and in situ cervical cancer.

  12. Uncontrolled illness not related to cancer, including but not limited to:

    • Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
    • Known uncontrolled human immunodeficiency virus (HIV) infection
    • Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration
  13. Blood or albumin transfusion within 5 days of the blood draw which has been used to confirm eligibility
  14. Pregnant or breast feeding
  15. Known hypsersensitivity to derazantinib, or to any of the study drug excipients (starch, lactose, crospovidone, magnesium stearate)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: derazantinib
Oral administration
Drug: derazantinib
Derazantinib was administered orally at 300 mg once daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Substudy 1: Objective Response Rate (ORR)
Time Frame: From first dose and up to 54 months
ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded independent central review using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1
From first dose and up to 54 months
Substudy 2: Progression Free Survival at 3 Months (PFS 3)
Time Frame: From first dose and up to 3 months
PFS3 was defined as the proportion of patients who have progression-free survival at 3 months from the first date of receiving study drug as assessed by survival status and blinded independent central review as per RECIST 1.1.
From first dose and up to 3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: From first dose and up to 54 months
PFS was calculated from the first date of receiving study drug until radiographic disease progression by blinded independent central review or death.
From first dose and up to 54 months
Overall Survival (OS)
Time Frame: From first dose and up to 54 months
OS was calculated from the first date of receiving study drug until death
From first dose and up to 54 months
Duration of Response (DoR)
Time Frame: From first dose and up to 54 months
DoR was calculated from the first date of documented tumor response to disease progression by blinded independent central review per RECIST version 1.1 DoR was derived only for patients who have the best overall response of CR or PR
From first dose and up to 54 months
Substudy 2: Objective Response Rate
Time Frame: From first dose and up to 54 months
ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded independent central review using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1
From first dose and up to 54 months
Number of Patients With Grade 3-5 Treatment-emergent Adverse Events (TEAEs)
Time Frame: TEAEs were defined as all events occurring after drug treatment began and up to 30 days after last study drug administration
Number of patients experiencing TEAE of Grade 3 to 5 according to Common Terminology Criteria for Adverse Events (CTCAE)
TEAEs were defined as all events occurring after drug treatment began and up to 30 days after last study drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Basilea Pharmaceutica

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Manuel Häckl, MD, Basilea Pharmaceutica International Ltd, Allschwil

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 28, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 25, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 25, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 24, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 26, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 19, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 29, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DZB-CS-301
  • ARQ 087-301 (Other Identifier: ArQule, Inc)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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