Inoperable Cholangiocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864
Conditions
Interventions
Product Name: Amphinex
Pharmaceutical Form: Solution for injection
INN or Proposed INN: fimaporfin
CAS Number: 1443547-43-0
Other descriptive name: Fimaporfin di-olamine
Concentration unit: mg/ml mill
Sponsors
PCI Biotech AS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements; 2. Male or female patient =18 years of age; 3. Cholangiocarcinoma verified as adenocarcinoma by histopathology or cytology with a perihilar or distal stenosis that has been stented or will require stenting, and that is accessible for PCI light treatment; 4. Cholangiocarcinoma must be considered inoperable with respect to radical resection (including partial liver resection or liver transplantation); 5. At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation; 6. If metastatic disease, metastasis must be limited to tissues other than bone or the central nervous system; 7. Adequate biliary drainage (at least 50% of the liver volume, or at least 2 sectors), with no evidence of active uncontrolled infection (patients on antibiotics are eligible); 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 9. Estimated life expectancy of at least 12 weeks. 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 49 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 137
Exclusion criteria
Exclusion criteria: 1. Previously received any anti-tumour (either local or systemic) treatment for CCA except for previous treatment of up to 2 cycles of gemcitabine/cisplatin; 2. Severe visceral disease other than CCA; 3. A history of frequently recurring septic biliary events; 4. Porphyria or hypersensitivity to porphyrins; 5. A second primary cancer, with a disease-free interval of <5 years. A second primary cancer that has been treated with intent to cure may be allowed after consultation with the study Medical Monitor. Adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, in situ carcinoma of the uterine cervix, or prostate cancer that is controlled by hormone therapy (patients may continue hormone therapy while on study) are allowed; 6. Unable to undergo contrast-enhanced CT or MRI; 7. Currently participating in any other interventional clinical study; 8. Planned surgery, endoscopic examination, or dental treatment in the first 30 days after PCI treatment; 9. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment; 10. 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, except for extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation; 11. Known allergy or sensitivity to photosensitisers, (the active substance and/or any of the excipients); or chronic use of other photosensitising therapies (Section 5.5.3); treatment with amiodarone during the last 12 months; 12. Known hypersensitivity to or contraindication to the use of gemcitabine (the active substance and/or any of the excipients); 13. Known hypersensitivity, or contraindication to the use of cisplatin (the active substance and/or any of the excipients); 14. Ataxia telangiectasia; 15. Upon the Investigator’s discretion, evidence of any other medical conditions (such as psychiatric illness, 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; 16. Plans to have, or has recently had, vaccination with a live vaccine, including for yellow fever; 17. Concurrently receiving treatment with phenytoin; 18. Male patients unwilling to use highly effective contraception or women of childbearing potential (WOCBP) unwilling to use a highly effective form of contraception such as the following: - Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal and transdermal) - Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable) - Intrauterine devices - Intrauterine hormone-releasing system - Bilateral tubal ligation - Vasectomised partner - Sexual abstinence Patients must continue the use of contraception during PCI treatment and subsequent chemotherapy, and for at least 9 months after last dose of Amphinex or 6 months after last dose of chemotherapy, whichever is the latest. 19. Breastfeeding women or women with a positive pregnancy test at baseline; 20. Inadequate bone marrow function as evidenced by one of the following: - Absolute neutrophil count (ANC) <1.5 × 109/L - Platelet count <100 × 109
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - to assess the efficacy of fimaporfin induced PCI of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy versus gemcitabine/cisplatin alone in patients with inoperable CCA by assessment of PFS;Timepoint(s) of evaluation of this end point: every 12 weeks;Secondary Objective: 1. To assess the longer-term efficacy in patients with inoperable CCA by assessment of OS; 2. To further assess of best overall response (BOR), objective response rate (ORR), duration of response (DoR), disease control rate (DCR) at 6 and 12 months, and change in tumour size per Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1); 3. To assess the effects of fimaporfin-induced PCI on safety in terms of loco regional tumour related events and biliary complications; 4. To further assess the safety profile (adverse events [AEs], laboratory assessments, physical findings, and photosensitivity) 5. To further characterise the pharmacokinetic (PK) profile of fimaporfin in plasma; 6. To assess the health-related quality of life (HRQoL) and patient reported outcome (PRO) measures;Primary end point(s): Progression free survival is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival: Overall survival (OS) is calculated as the time from randomisation to the date of death from any cause. Best Overall Response: The BOR is the best response recorded from the start of the treatment until disease progression/recurrence. Objective Response Rate: The ORR is calculated as the proportion of patients who have at least one visit response with a CR or PR noted. Duration of Response: The DoR is defined as the time from the first documented tumour response until radiological disease progression, or death in the absence of disease progression. Disease Control Rate: The DCR is defined as the proportion of patients with stable disease or better (CR, PR or SD); assessed at 6 and 12 months.;Timepoint(s) of evaluation of this end point: every 12 weeks | — |
Countries
Belgium, Denmark, Finland, France, Germany, Italy, Korea, Republic of, Norway, Poland, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactRoberta Fumagalli - PM
PPD
Outcome results
None listed