A study to investigate the effects of the drug derazantinib (formerly ARQ 087) in patients who have a type of bile duct cancer that cannot be operated on, or has spread, called Advanced Intrahepatic Cholangiocarcinoma. Patients will have a positive genetic test for FGFR2 Gene Fusion or FGFR2 gene mutations or amplifications.
- Conditions
- Substudy 1Inoperable or advanced FGFR2 gene fusion positive iCCASubstudy 2:Inoperable or advanced iCCA harboring FGFR2 mutations or amplificationsMedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10073078Term: Intrahepatic cholangiocarcinoma recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004448-12-GB
- Lead Sponsor
- Basilea Pharmaceutica International Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 143
Tissue samples for genetic testing will be obtained from subjects who meet the following pre-screening eligibility criteria:
1. Signed written informed consent to permit tissue analysis
2. 18 years of age or older
3. No medical history that is excluded per the study treatment eligibility criteria
4. Eastern Cooperative Oncology Group (ECOG) performance status = 1 (Appendix 2)
5. Eligible for or receiving systemic therapy for inoperable or advanced iCCA
6. Not currently eligible for curative local or surgical therapy
To be enrolled in the study, once the FGFR2 genomic aberration status is determined, each prospective subject must meet all of the following inclusion criteria and none of the exclusion 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. Substudy 1:
FGFR2 gene fusion status based on the following assessments:
a) If central laboratory designated by the 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**
* Using standard protocols and approved by local IRB/IEC, CLIA, or other similar agency. For enrollment of patients in the EU, assays must be fully CE-marked.
** The patient must not be enrolled if a negative FISH test is obtained from the central laboratory prior to commencing study treatment. Patients without central confirmation of an FGFR2 fusion by the central FISH test will be assessed on a case-by-case basis.
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
Substudy 2:
FGFR2 mutation status based on local NGS testing performed or commissioned by the respective study site using a validated test listed Section 6.7. For enrollment of patients in the EU, assays must be fully CE-marked. For NGS testing, no central laboratory will be established for the purpose of Substudy 2.
5. Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression (for Substudy 1), and have no satisfactory treatment alternatives (for Substudy 2).
6. Measurable disease by RECIST version 1.1 criteria
7. ECOG performance status = 1 (Appendix 2 of protocol)
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 to the power of 9/L
? Platelet count = 75 x 10 to the power of 9/L
? International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or = 3 for subjects receiving anticoagulant therapy such as warfarin or heparin
- Hepatic
? Total bilirubin = 2 x ULN
? Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 ULN (= 5 x ULN for subjects with liver metastases)
? Albumin = 2.8 g/dL
- Renal
? Serum creatinine = 1.5 x ULN, or
? Creatinine clearance of = 60 mL/min as estimated by the Cockcroft-Gault equation
9. Female and male patients of child-producing potenti
1. 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 the respective anticancer therapy, whichever is the longer period.
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 [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 derazantinib (MI that occurred > 6 months prior to the first dose of derazantinib are permitted)
- QTcF > 450 msec for men and QTcF > 460 msec for women
9.Serum electrolyte abnormalities defined as follows:
• Hyperphosphatemia: serum phosphate > institutional ULN
•Hyperkalemia: serum potassium > institutional ULN
•Hypokalemia: serum potassium < institutional lower limit of normal (LLN)
• Hypercalcemia: corrected serum calcium > 3.1 mmol/L (>12.5 mg/dL)
• Hypocalcemia: corrected serum calcium < 1.75 mmol/L (<7.0 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. 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
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
13. Blood or albumin transfusion within 5 days of the blood draw being used to confirm eligibility
14. Pregnant or breast feeding
15. Known hypsersensitivity to derazantinib, or to any of the study drug excipients (starch, lactose, crospovidone, magnesium stearate).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method