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Intrahepatic CholangiocarcinomaPhase 2FIDES-01NCT03230318

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

A Phase 2 study testing derazantinib in people with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular and Cholangiocarcinoma, run by Basilea Pharmaceutica at 41 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
derazantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
148 participants
Where
41 sitesin 11 countries
Study dates
28 Sep 2017to 25 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent granted prior to initiation of any study-specific procedures
  • 18 years of age or older
  • Histologically or cytologically confirmed locally advanced, inoperable, or metastatic iCCA or mixed histology tumors
  • Substudy 1:
  • FGFR2 fusion status based on the following assessments:
  • 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
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  • 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.
  • Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression
  • Measurable disease by RECIST version 1.1 criteria
  • ECOG performance status ≤ 1
  • 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
  • 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:
  • Abstinence from heterosexual activity
  • Using (or having their partner use) an acceptable method of contraception during heterosexual activity.

Who cannot join

  • 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
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  • 28 days of radiotherapy
  • Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of derazantinib
  • Previous treatment with any FGFR inhibitor (e.g., Balversa® [erdafitinib], Pemazyre® [pemigatinib], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib, dovitinib, nintedanib, AZD4547, LY2784455).
  • Patients who were unable or unwilling to swallow the complete daily dose of derazantinib capsules
  • 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)
  • 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.
  • 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)
  • 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)
  • 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)
  • 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)
  • 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.
  • 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
  • Blood or albumin transfusion within 5 days of the blood draw which has been used to confirm eligibility
  • Pregnant or breast feeding
  • Known hypsersensitivity to derazantinib, or to any of the study drug excipients (starch, lactose, crospovidone, magnesium stearate)

Trial locations and contacts

41 sites in 11 countries.

41 sites in 11 countries

United States11 sites
  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center for Prostate and Urologic Cancers

    New York, New York, 10065-6800

  • Abramson Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Washington Medical Center

    Seattle, Washington, 98109

  • Moffitt Cancer Center

    Tampa, Florida, 33612-9416

Other trials in United States

Italy6 sites
  • Sant'Orsola-Malpighi Hospital, University of Bologna

    Bologna, 40138

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • Ospedale San Gerardo

    Monza, 20900

  • Istituto Oncologico Veneto - IRCCS

    Padova, 35128

  • Azienda Ospedaliero-Universitaria Pisana

    Pisa, 56126

  • Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS

    Rozzano, 20089

Other trials in Italy

Germany5 sites
  • Universitätsklinikum Frankfurt

    Frankfurt am Main, 60590

  • Universitätsklinikum Hamburg-Eppendorf (UKE)

    Hamburg, 20246

  • Medizinische Hochschule Hannover (MHH)

    Hanover, 30625

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz

    Mainz, 55131

Other trials in Germany

Spain4 sites
  • Vall d'Hebrón University Hospital

    Barcelona, 08035

  • Catalan Institute of Oncology

    Barcelona, 08908

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

Other trials in Spain

Belgium3 sites
  • Hôpital Erasme

    Brussels, 1070

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

  • Antwerp University Hospital

    Edegem, 2650

Other trials in Belgium

South Korea3 sites
  • Seoul National University Hospital

    Seoul, 3080

  • Samsung Medical Center

    Seoul, 6351

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 6591

Other trials in South Korea

United Kingdom3 sites
  • University College London Hospitals NHS Foundation Trust

    Euston, NW1 2BU

  • Beatson West of Scotland Cancer Centre

    Glasgow, G120YN

  • The Royal Marsden

    Sutton, SM2 5PT

Other trials in United Kingdom

Canada2 sites
  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

France2 sites
  • CHU Grenoble Alpes

    La Tronche, 38700

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

Ireland1 site
  • St. James's Hospital

    Dublin, D08 NHY1

Other trials in Ireland

Switzerland1 site
  • Universitätsspital Basel

    Basel, 4031

Other trials in Switzerland

About this study

Official title: 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.

Read the 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.

Being tested
derazantinib
Keywords
iCCA, intrahepatic cholangiocarcinoma, FGFR2 gene fusion or FGFR2 gene mutation or amplification, biliary cancer, bile duct cancer, FGFR2 gene rearrangement, liver cancer, targeted therapy, combined hepatocellular and cholangiocarcinoma, cHCC-CCA, derazantinib
Medical subject headings
Cholangiocarcinoma, Liver Neoplasms, Biliary Tract Neoplasms, Bile Duct Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • derazantinibDrug

    Derazantinib was administered orally at 300 mg once daily

Study groups in NCT03230318
Study groupRoleWhat they receive
derazantinibExperimentalOral administration
Receives: Drug: derazantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Substudy 1: Objective Response Rate (ORR)

    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

    Measured: From first dose and up to 54 months

  2. Substudy 2: Progression Free Survival at 3 Months (PFS 3)

    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.

    Measured: From first dose and up to 3 months

Secondary outcomes (5)
  1. PFS

    PFS was calculated from the first date of receiving study drug until radiographic disease progression by blinded independent central review or death.

    Measured: From first dose and up to 54 months

  2. Overall Survival (OS)

    OS was calculated from the first date of receiving study drug until death

    Measured: From first dose and up to 54 months

  3. Duration of Response (DoR)

    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

    Measured: From first dose and up to 54 months

  4. Substudy 2: Objective Response Rate

    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

    Measured: From first dose and up to 54 months

  5. Number of Patients With Grade 3-5 Treatment-emergent Adverse Events (TEAEs)

    Number of patients experiencing TEAE of Grade 3 to 5 according to Common Terminology Criteria for Adverse Events (CTCAE)

    Measured: TEAEs were defined as all events occurring after drug treatment began and up to 30 days after last study drug administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2017
  2. Study start28 Sep 2017
  3. Primary completion25 Oct 2022
  4. Study completion25 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
148 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03230318
Sponsor's protocol ID
DZB-CS-301
Other IDs
ARQ 087-301
Acronym
FIDES-01
Status last verified
Nov 2023
First submitted
24 Jul 2017
Last updated
19 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Mazzaferro V, El-Rayes BF, Droz Dit Busset M, Cotsoglou C, Harris WP, Damjanov N, Masi G, Rimassa L, Personeni N, Braiteh F, Zagonel V, Papadopoulos KP, Hall T, Wang Y, Schwartz B, Kazakin J, Bhoori S, de Braud F, Shaib WL. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019 Jan;120(2):165-171. doi: 10.1038/s41416-018-0334-0. Epub 2018 Nov 13.

    PubMed 30420614

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing derazantinib in people with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular and Cholangiocarcinoma, run by Basilea Pharmaceutica at 41 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States, Italy, Germany, Spain, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Substudy 1: Objective Response Rate (ORR) (time frame: From first dose and up to 54 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03230318, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.

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