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



November 2017

Letztes Update:


Indikation (Clinical Trials):
Cholangiocarcinoma, Carcinoma, Hepatocellular


Erwachsene (18+)

Phase 2

Basilea Pharmaceutica



Stephan Braun, MD
Study Director
Basilea Pharmaceutica


(3 von 40)

Universitätsklinikum Frankfurt
60590 Frankfurt am Main
GermanyRekrutierend» Google-Maps
Oliver Waidmann, PI

Studienambulanz Medizinische Klinik 1
Phone: +49 69 6301 87769
» Ansprechpartner anzeigen
Universitätsklinikum Hamburg-Eppendorf (UKE)
20246 Hamburg
GermanyRekrutierend» Google-Maps
Henning Wege, PI

University Medical Center Hamburg-Eppendorf
Phone: +49 40 7410 57981
» Ansprechpartner anzeigen
Medizinische Hochschule Hannover (MHH)
30625 Hannover
GermanyNoch nicht rekrutierend» Google-Maps
Universitäts-Brustzentrum am Universitätsklinikum des Saarlandes
Kirrberger Straße 100
66424 Homburg
DeutschlandRekrutierend» Google-Maps
Universitätsklinikum des Saarlandes Klinik für Innere Medizin II (Studienbüro)
Phone: +49 684116 15288

Phone: +49 684116 15289
» Ansprechpartner anzeigen
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
55131 Mainz
GermanyRekrutierend» Google-Maps
Moffitt Cancer Center
33612-9416 Tampa
United StatesNoch nicht rekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center for Prostate and Urologic Cancers
10065-6800 New York
United StatesRekrutierend» Google-Maps
Abramson Cancer Center of the University of Pennsylvania
19104 Philadelphia
United StatesRekrutierend» Google-Maps
Vanderbilt-Ingram Cancer Center
37232 Nashville
United StatesRekrutierend» Google-Maps
The University of Texas Southwestern Medical Center
75390 Dallas
United StatesRekrutierend» Google-Maps
University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
University of Washington Medical Center
98109 Seattle
United StatesRekrutierend» Google-Maps
Hôpital Erasme
1070 Brussels
BelgiumRekrutierend» Google-Maps
Anne Demols, PI

Axelle Ghilain, Study Coordinator
Phone: +32 2 555 44 55
» Ansprechpartner anzeigen
Cliniques Universitaires Saint-Luc
1200 Brussels
BelgiumRekrutierend» Google-Maps
Antwerp University Hospital
2650 Edegem
BelgiumRekrutierend» Google-Maps
Marc Peeters, PI

Peggy De Clercq, Study Coordinator
Phone: +32 3 821 53 07
» Ansprechpartner anzeigen
Princess Margaret Cancer Centre
M5G 2M9 Toronto
CanadaRekrutierend» Google-Maps
Sant'Orsola-Malpighi Hospital, University of Bologna
40138 Bologna
ItalyRekrutierend» Google-Maps
Giovanni Brandi, PI

Marzia Deserti, Study Coordinator
» Ansprechpartner anzeigen
Fondazione IRCCS Istituto Nazionale dei Tumori
20133 Milan
ItalyRekrutierend» Google-Maps
Vincenzo Mazzaferro, PI

Emanuela Mazzella, Study Coordinator
Phone: +39 02 23902544
» Ansprechpartner anzeigen
Istituto Oncologico Veneto - IRCCS
35128 Padova
ItalyRekrutierend» Google-Maps
Azienda Ospedaliero-Universitaria Pisana
56126 Pisa
ItalyRekrutierend» Google-Maps
Gianluca Masi, PI

Cenar Ahmed, Study Coordinator
Phone: +39 050 99 3841
» Ansprechpartner anzeigen
Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS
20089 Rozzano
ItalyRekrutierend» Google-Maps
Nicola Personeni, PI

Simona Sala, Study Coordinator
» Ansprechpartner anzeigen
The Catholic University of Korea, Seoul St. Mary's Hospital
6591 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Myung-Ah Lee, PI

Hyunjoo An, Study Coordinator
» Ansprechpartner anzeigen
Hospital General Universitario Gregorio Marañón
28007 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario 12 de Octubre
28041 Madrid
SpainRekrutierend» Google-Maps
The Royal Marsden
SM2 5PT Sutton
United KingdomRekrutierend» Google-Maps
David Cunningham, PI

Linda Kirkwood, Study Coordinator
Phone: +44 208 661 3637
» Ansprechpartner anzeigen
Alle anzeigen


Brief Summary:

This pivotal, open-label, single-arm study will evaluate the anti-cancer activity of

derazantinib by Objective Response Rate (ORR) by central radiology review as per RECIST v1.1

in subjects with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) whose tumors

harbor FGFR2 gene fusions (by FISH performed by the central laboratory) or FGFR2 gene

mutations or amplifications (based on NGS testing performed or commissioned by the respective

study center) and who received at least one prior regimen of systemic therapy. Subjects will

be dosed orally once per day at 300 mg of derazantinib capsules.


Inclusion Criteria:

1. Signed written informed consent granted prior to initiation of any study-specific


2. 18 years of age or older

3. Histologically or cytologically confirmed locally advanced, inoperable (where surgery

is not indicated due to disease extension, co-morbidities, or other technical

reasons), or metastatic iCCA or mixed histology tumors (combined

hepatocellular-cholangiocarcinoma [cHCC-CCA])

4. Substudy 1: FGFR2 gene fusion status based on the following assessments:

a) If central laboratory designated by Sponsor: Positive FISH test; and/or b) If

non-central laboratory: i) Positive FISH or NGS test: patients may be enrolled and may

start dosing, but central confirmation is required* ii) Negative FISH or NGS test:

tissue may be submitted to the central laboratory designated by the Sponsor, and

patients may only be enrolled if the central test is positive

*Using standard protocols and approved by local IRB/EC, by CLIA or other similar


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 receiving 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


9. Female and male patients of child-producing potential must agree to avoid becoming

pregnant or impregnating a partner, respectively, use double-barrier contraceptive

measures, oral contraception, or avoidance of intercourse, during the study*, and

until at least 120 for 90 days after the last dose of derazantinib.

*From the day of first study medication, or for oral contraception from 14 days before

first study medication.

Male patients are considered not to be of child-producing potential if they have

azoospermia (whether due to vasectomy or an underlying medical condition). Female

patients are considered not to be of child-producing potential if they are:

- postmenopausal* , or

- have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or

bilateral tubal ligation/occlusion, at least 6 weeks prior to screening, or

- have a congenital or acquired condition that prevents childbearing.

Male or female patients of child-producing potential must agree 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. Acceptable methods of contraception are***:

- any ONE of:

- an intrauterine device (IUD)

- vasectomy of a female patient's male partner

- a contraceptive rod implanted into the skin.

- any TWO in combination of:

- diaphragm with spermicide (cannot be used in conjunction with cervical


- cervical cap with spermicide (nulliparous women only)

- contraceptive sponge (nulliparous women only)

- male condom or female condom (cannot be used together)

- hormonal contraceptive (oral contraceptive pill [estrogen/progestin pill

or progestin-only pill], contraceptive skin patch, vaginal contraceptive

ring, or subcutaneous contraceptive injection)

*Postmenopausal is defined as at least 12 months with no menses without an

alternative medical cause; in women < 45 years of age a high follicle

stimulating hormone (FSH) level in the postmenopausal range may be used to

confirm a post -menopausal state in women not using hormonal contraception

or hormonal replacement therapy. In the absence of 12 months of amenorrhea,

a single FSH measurement is not sufficient.

- Abstinence (relative to heterosexual activity) can be used as the sole

method of contraception if it is consistently employed as the subject's

preferred and usual lifestyle and if considered acceptable by local

regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar,

ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal

are not acceptable methods of contraception.

- If a contraceptive method listed above is restricted by local

regulations/guidelines, then it does not qualify as an acceptable

method of contraception for subjects participating at sites in

this country/region.

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


- 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).

- Subjects who received less than four weeks of therapy and were unable to continue

therapy due to toxicity will be allowed to participate

4. 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 have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or

computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose

steroids, anti-epileptics, or other symptom-relieving medications)

6. Current evidence of clinically significant corneal or retinal disorder 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. Concurrent 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 have to

be treated and disorders/complications should be 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 will be 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, in the opinion of the

Investigator, interfere with the absorption, metabolism, or excretion of derazantinib

(e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)

11. History of additional malignancy that is progressing or requires active treatment.

Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the

skin that has undergone potentially curative therapy, and in situ cervical cancer.

12. Concurrent 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 being used to confirm


14. Pregnant or breast feeding

15. Known hypsersensitivity to derazantinib, or to any of the study drug excipients

(starch, lactose, crospovidone, magnesium stearate)


Primary outcome:

1. Substudy 1: Anti-cancer activity of derazantinib by Objective Response Rate (ORR) (Time Frame - Up to approximately 32 weeks):
ORR will be assessed by central radiology review as per RECIST version 1.1

2. Substudy 2: Anti-tumor activity of derazantinib by Progression Fress Survival at 3 months (PFS 3) (Time Frame - 3 months):
PFS 3 will be assessed based on survival status or central radiology review (Response Evaluation Criteria in Solid Tumors, RECIST 1.1)

Secondary outcome:

1. Safety of derazantinib as assessed by adverse events (Time Frame - Up to approximately 36 weeks):
Adverse events will be graded using NCI CTCAE guidelines, version 4.03

2. Anti-cancer activity of derazantinib by duration of response (DoR) (Time Frame - Up to approximately 32 weeks):
DoR will be assessed by central radiology review per RECIST version 1.1

3. Anti-cancer activity of derazantinib by progression free survival (PFS) (Time Frame - Up to approximately 32 weeks):
PFS will be assessed by central radiology review per RECIST version 1.1

4. Anti-cancer activity of derazantinib by overall survival (OS) (Time Frame - Up to approximately 36 weeks):
OS will be calculated from the first date of receiving study drug until death

5. Health-related quality of life as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (Time Frame - Up to approximately 36 weeks)

6. Health-related quality of life as assessed by the EORTC QLQ-BIL21 questionnaire (Time Frame - Up to approximately 36 weeks)

7. Health-related quality of life as assessed by the EuroQol EQ-5D questionnaire (Time Frame - Up to approximately 36 weeks)

8. Substudy 2: Anti-cancer activity of derazantinib by Objective Response Rate (Time Frame - Up to approximately 32 weeks):
ORR will be assessed by central radiology review as per RECIST version 1.1

Geprüfte Regime

  • derazantinib:
    derazantinib will be orally administered at 300 mg once per day one hour prior to or two hours after a meal and is supplied as 100 mg capsules.


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