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

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ClinicalTrials.gov Identifier: NCT03230318
Recruitment Status : Recruiting
First Posted : July 26, 2017
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Basilea Pharmaceutica

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) 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.

Condition or disease Intervention/treatment Phase
Intrahepatic Cholangiocarcinoma Combined Hepatocellular and Cholangiocarcinoma Drug: derazantinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pivotal Trial of Derazantinib in Subjects With FGFR2 Gene Fusion Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma
Actual Study Start Date : November 10, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Experimental: derazantinib
Oral administration
Drug: 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.




Primary Outcome Measures :
  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 per RECIST version 1.1


Secondary Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (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. FGFR2 gene fusion status based on the following assessments:

    1. If central laboratory designated by Sponsor:

      Positive FISH test; and/or

    2. 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.

  5. Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression or was not able to tolerate prior systemic therapy.

    • If the subject received at least 4 cycles of systemic therapy and no measurable tumor reduction compared to the previous scan is observed, such subject can be enrolled
    • If the subject received immunotherapy, the documented radiographic disease progression is required
  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 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
  9. Male or female subjects of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after the last dose of derazantinib

Exclusion Criteria:

  1. Systemic anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks of the first dose of derazantinib
  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., 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

  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 corneal or retinal disorder, including but not limited to bullous/band keratopathy, keratoconjunctivitis, 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 >500 msec (males or females)
  9. 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)
  10. 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
  11. 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
  12. Blood or albumin transfusion within 5 days of the blood draw being used to confirm eligibility
  13. Pregnant or breast feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03230318


Contacts
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Contact: Stephan Braun, MD +41 61 606 12 25 stephan.braun@basilea.com
Contact: Frédérique Cantero, MD +41 61 606 1329 frederique.cantero@basilea.com

Locations
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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98109
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Italy
A.O. "G. Rummo" Not yet recruiting
Benevento, Italy, 82100
Sant'Orsola-Malpighi Hospital, University of Bologna Recruiting
Bologna, Italy, 40138
Fondazione IRCCS Istituto Nazionale dei Tumor Recruiting
Milan, Italy, 20133
Istituto Oncologico Veneto - IRCCS Recruiting
Padova, Italy, 35128
Azienda Ospedaliero-Universitaria Pisana Recruiting
Pisa, Italy, 56126
Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS Recruiting
Rozzano, Italy, 20089
Sponsors and Collaborators
Basilea Pharmaceutica
Investigators
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Study Director: Stephan Braun, MD Basilea Pharmaceutica

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Responsible Party: Basilea Pharmaceutica
ClinicalTrials.gov Identifier: NCT03230318     History of Changes
Other Study ID Numbers: DZB-CS-301
ARQ 087-301 ( Other Identifier: ArQule, Inc )
First Posted: July 26, 2017    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Basilea Pharmaceutica:
iCCA
intrahepatic cholangiocarcinoma
FGFR2 gene fusion
biliary cancer
bile duct cancer
FGFR2 gene rearrangement
liver cancer
targeted therapy
combined hepatocellular and cholangiocarcinoma
cHCC-CCA
derazantinib

Additional relevant MeSH terms:
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Cholangiocarcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases