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 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-DE
- Lead Sponsor
- Basilea Pharmaceutica International Ltd, Allschwil
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 147
Tissue samples for genetic testing will be obtained from patients 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
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 patient 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 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, Clinical Laboratory Improvement Amendments (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 mutations/amplifications without any concurrent FGFR2 translocations 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 (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 = 30 mL/min as estimated by the Cockcroft-Gault equation
9. Female and male patients of child-producing potential must agree to avoid becoming pregnant or impregnating a partner, respectively during the study, and for at least 120 days after the last dose of derazantini
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 product
- 2 weeks, for any investigational medicinal product with an unknown half-life
- 4 weeks of curative radiotherapy
- 7 days of palliative radiotherapy
- 28 days of radiotherapy
2. Major surgery or locoregional therapy within 4 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)
4. Unable or unwilling to swallow the complete daily dose of derazantinib capsules
5. Clinically unstable central nervous system (CNS) metastases (to be eligible, patients 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 are permitted)
- QTcF > 450 msec for men and QTcF > 460 msec for women
9.Serum electrolyte abnormalities defined as follows:
• Hyperphosphatemia: serum phosphate > institutional upper limit of normal (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. 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 under t
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