Clinical Trials /

Derazantinib in Subjects With FGFR2 Gene Fusion Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

NCT03230318

Description:

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.

Related Conditions:
  • Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ARQ 087 in Subjects With FGFR2 Gene Fusion Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma
  • Official Title: A Pivotal Trial of ARQ 087 in Subjects With FGFR2 Gene Fusion Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: ARQ 087-301
  • NCT ID: NCT03230318

Conditions

  • Intrahepatic Cholangiocarcinoma
  • Combined Hepatocellular and Cholangiocarcinoma

Interventions

DrugSynonymsArms
ARQ 087ARQ 087

Purpose

This pivotal, open-label, single-arm study will evaluate the anti-cancer activity of ARQ 087 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 ARQ 087 capsules.

Trial Arms

NameTypeDescriptionInterventions
ARQ 087Experimental
  • ARQ 087

Eligibility 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 confirmed by NGS or FISH testing

               -  Test positive by FISH by the central laboratory designated by the Sponsor

               -  Have FGFR2 gene fusion documented by a local or central laboratory using standard
                  protocols and approved by local IRB/EC, by CLIA or other similar agency. If the
                  FGFR2 gene fusion is identified by a laboratory other than the Sponsor's central
                  laboratory, then archival and/or recent tissue biopsy samples or a tissue block
                  suitable for genetic testing must be available for confirmatory testing by FISH
                  by the Sponsor's central laboratory. If a subject has documentation from the
                  central laboratory indicating that they test negative for FGFR2 gene fusion, that
                  subject may not be enrolled in the study.

          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

          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 ARQ 087

        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 ARQ 087

          2. Major surgery, locoregional therapy, or radiation therapy within four weeks of the
             first dose of ARQ 087

          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 ARQ 087 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 ARQ 087)

          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 ARQ 087 (MI that occurred > 6 months prior to the first dose of ARQ
                  087 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 ARQ 087
             (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)

         10. Previous malignancy within 2 years of the first dose of ARQ 087, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Anti-cancer activity of ARQ 087 by Objective Response Rate (ORR)
Time Frame:Up to approximately 32 weeks
Safety Issue:
Description:ORR will be assessed by central radiology review per RECIST version 1.1

Secondary Outcome Measures

Measure:Safety of ARQ 087 as assessed by adverse events
Time Frame:Up to approximately 36 weeks
Safety Issue:
Description:Adverse events will be graded using NCI CTCAE guidelines, version 4.03
Measure:Anti-cancer activity of ARQ 087 by progression free survival (PFS)
Time Frame:Up to approximately 32 weeks
Safety Issue:
Description:PFS will be assessed by central radiology review per RECIST version 1.1
Measure:Anti-cancer activity of ARQ 087 by overall survival (OS)
Time Frame:Up to approximately 36 weeks
Safety Issue:
Description:OS will be calculated from the first date of receiving study drug until death
Measure:Anti-cancer activity of ARQ 087 by duration of response (DoR)
Time Frame:Up to approximately 32 weeks
Safety Issue:
Description:DoR will be assessed by central radiology review per RECIST version 1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ArQule

Trial Keywords

  • iCCA
  • intrahepatic cholangiocarcinoma
  • FGFR2 gene fusion
  • ARQ 087
  • biliary cancer
  • bile duct cancer
  • FGFR2 gene rearrangement
  • liver cancer
  • targeted therapy
  • combined hepatocellular and cholangiocarcinoma
  • cHCC-CCA

Last Updated

February 21, 2018