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A Pivotal Study of Derazantinib in Patients With Inoperable or Advanced Intrahepatic Cholangiocarcinoma and FGFR2 Gene Fusions or FGFR2 Gene Mutations or Amplifications (FIDES-01)

Studio Clinico

Patologia: Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: II

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

  • 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 (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])
  • Substudy 1: FGFR2 gene fusion status based on the following assessments:
       If central laboratory designated by Sponsor:
       - Positive FISH test; and/or
       - 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 agency.
    Substudy 2: FGFR2 mutation status based on local NGS testing performed or commissioned by the respective study site using a validated test. For NGS testing, no central laboratory will be established for the purpose of Substudy 2.
  • 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 109/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 ≥ 60 mL/min as estimated by the Cockcroft-Gault equation
  • 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:
      - Abstinence from heterosexual activity**
      - 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 cap/spermicide)
         • 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.

Criteri di esclusione: 

  • Systemic anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks of the first dose of derazantinib, or within five half-lives of any investigational or licensed medicinal product, whichever is the longer period.
  • Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of derazantinib
  • Previous treatment with any FGFR inhibitor (e.g., ponatinib, dovitinib, nintedanib, AZD4547, NVP-BGJ398, LY2784455, BAY1163877)
    - Subjects who received less than four weeks of therapy and were unable to continue therapy due to toxicity will be allowed to participate
  • Unable or unwilling to swallow the complete daily dose of derazantinib capsules
  • 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)
  • Current evidence of corneal or retinal disorder, including but not limited to bullous/band keratopathy, keratoconjunctivitis, corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination
  • 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)
  • 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)
  • 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, 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)
  • Previous malignancy within 2 years of the first dose of derazantinib, except curatively treated or low grade malignancies such as non-melanoma skin cancer, carcinoma in-situ of the breast, cervix, and superficial bladder tumors
  • 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
  • Blood or albumin transfusion within 5 days of the blood draw being 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).

Trattamento sperimentale: 

Derazantinib

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- Substudy 1: Anti-cancer activity of derazantinib by Objective Response Rate (ORR) [Time Frame: Up to approximately 32 weeks]
- Substudy 2: Anti-tumor activity of derazantinib by Progression Fress Survival at 3 months (PFS 3) [Time Frame: 3 months]

Centri partecipanti

Nord Italia

Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO

 

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI

Riferimento: Prof. Vincenzo Mazzaferro
Telefono: 0223902338
Email: vincenzo.mazzaferro@istitutotumori.mi.it

 

Istituto Clinico Humanitas Rozzano
Via Manzoni 56 - 20089 Rozzano - MI

 

A.O. San Gerardo
Via Pergolesi 33 - 20900 Monza - MB
NB: Arruolamento pazienti non ancora attivo

 

Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD

 

Centro Italia

AOU Pisana - Santa Chiara
Via Roma 67 - 56126 Pisa - PI

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2016-004448-12

Data di inserimento: 08.06.2020

Promotore

Basilea Pharmaceutica

CRO

Covance

Principal Investigator ITALIA

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Riferimento: Prof. Vincenzo Mazzaferro

Telefono: 0223902338

Email: vincenzo.mazzaferro@istitutotumori.mi.it

Localita: Milano

 

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