Inoperable advanced cholangiocarcinomas MedDRA version: 20.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000054936
Conditions
Interventions
Product Name: Amphinex
Pharmaceutical Form: Solution for injection
INN or Proposed INN: fimaporfin
CAS Number: 1443547-43-0
Current Sponsor code: TPCS2a
Other descriptive name: AMPHINEX
Concentration
Sponsors
PCI Biotech AS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histopathologically/cytologically (C5) verified adenocarcinoma consistent with cholangiocarcinoma. 2. Cholangiocarcinoma that: A) Is considered to be inoperable B) Has a primary lesion in the perihilar biliary duct region that requires stent placement C) Has nodal enlargement =to N1 as per computed tomography/magnetic resonance imaging assessment D) If has metastatic disease, this should be confined to the liver parenchyma only 3. Adequate biliary drainage (either at least 50% of the liver volume, or at least two sectors), with no evidence of active uncontrolled infection (patients on antibiotics are eligible) 4. Age =18 years 5. The Eastern Cooperative Oncology Group performance status =1 6. Estimated life expectancy of at least 12 weeks 7. Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Any prior anti-cancer (either local or systemic) treatment for cholangiocarcinoma 2. Patients with extra-hepatic metastatic cholangiocarcinoma 3. Patients with a severe visceral disease other than cholangiocarcinoma. 4. Patients with primary sclerosing cholangitis 5. Patients with porphyria or hypersensibility to porphyrins 6. Patients with an active second primary cancer, with exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix. An active second primary cancer is defined as one with a disease-free interval of 2.5 x the upper limit of normal for the institution - Aspartate amino transferase or alanine amino transferase >3.0 x upper limit of normal (>5.0 x upper limit of normal if liver metastases are present) - Alkaline phosphatase levels >5.0 x upper limit of normal 13. Inadequate renal function, defined as: - Creatinine clearance <60 mL/min 14. Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment 15. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment 16. Clinically significant and uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to baseline, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation 17. Known allergy or sensitivity to photosensitisers 18. Ataxia telangiectasia 19. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the planned PCI treatment, affect patient compliance or place the patient at high risk from treatment-related complications 20. Significant hearing impairment 21. Patients concurrently receiving phenytoin 22. Patients defined as vulnerable according to French law (France only, also see Section 5.4
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I Dose Escalation • To determine a tolerable dose and safety profile of Amphinex-induced PCI of gemcitabine followed by systemic gemcitabine/cisplatin chemotherapy in patients with advanced inoperable cholangiocarcinoma Extended Part of Phase I • To determine the tolerability and safety profile of a two-administration schedule of Amphinex-induced PCI of gemcitabine followed by systemic gemcitabine/cisplatin chemotherapy in patients with advanced inoperable cholangiocarcinoma Phase II • To make a preliminary assessment of the efficacy of Amphinex-induced PCI of gemcitabine followed by systemic gemcitabine/cisplatin chemotherapy in patients with advanced inoperable cholangiocarcinoma ;Secondary Objective: Phase I Dose Escalation • To characterise the pharmacokinetic profiles of Amphinex and gemcitabine • To make a preliminary assessment of the efficacy of Amphinex-induced PCI of gemcitabine followed by systemic gemcitabine/cisplatin chemotherapy in patients with advanced inoperable cholangiocarcinoma Extended Part of Phase I • To characterise the pharmacokinetic profiles of Amphinex and gemcitabine • To make a preliminary assessment of the efficacy of a two-administration schedule of Amphinex-induced PCI of gemcitabine followed by systemic gemcitabine/cisplatin chemotherapy in patients with advanced inoperable cholangiocarcinoma Phase II • To characterise the pharmacokinetic profile of Amphinex • To further assess the safety and efficacy profile of Amphinex-induced PCI of gemcitabine followed by the systemic gemcitabine/cisplatin combination ;Primary end point(s): Phase I Dose Escalation (Safety) • Dose-limiting toxicities and the safety profile (adverse events, laboratory assessments and physical findings) of the Amphinex-induced PCI of gemcitabine followed by the gemcitabine/cisplatin combination Extended Part of Phase I (Safety) • Schedule-limiting toxicities and the safety profile (adverse events, laboratory assessments and physical fin | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I Dose Escalation • Pharmacokinetic profile of Amphinex and gemcitabine in plasma • Progression-free survival, defined as the time from registration to documented disease progression (according to RECIST 1.1 criteria) or death from any cause • Best overall response Extended Part of Phase I • Pharmacokinetic profile of Amphinex and gemcitabine in plasma • Progression-free survival, defined as the time from registration to documented disease progression (according to RECIST 1.1 criteria) or death from any cause • Best overall response at 24 weeks Phase II • Overall response rate, calculated as the proportion of patients with a best overall response of confirmed complete response or partial response • Disease control rate, defined as the proportion of patients with best overall response of confirmed complete response, partial response or stable disease • Overall survival, calculated as the time from randomisation to the date of death from any cause • Best overall response • Pharmacokinetic profile of Amphinex in bile • Safety profile (adverse events, laboratory assessments and physical findings) of the Amphinex-induced PCI of gemcitabine followed by the gemcitabine/cisplatin combination, or the gemcitabine/cisplatin combination alone ;Timepoint(s) of evaluation of this end point: Please refer to study protocol | — |
Countries
Austria, France, Germany, Lithuania, Norway, United Kingdom
Contacts
Public ContactRegulatory Affairs
Theradex (Europe) Ltd
Outcome results
None listed