E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inoperable Cholangiocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Bile duct cancer that cannot be removed with surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008594 |
E.1.2 | Term | Cholangiocarcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- 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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (C5) 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 the liver parenchyma and/or local lymph nodes (within close proximity to the hepatoduodenal ligament); 7. Adequate biliary drainage (either 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. |
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E.4 | Principal exclusion criteria |
1. Previously received any anti-tumour (either local or systemic) treatment for CCA; 2. Severe visceral disease other than CCA; 3. A history of frequently recurring septic biliary events caused by non-malignant strictures (primary sclerosing cholangitis [PSC], autoimmune hepatitis or advanced chronic liver dysfunction); 4. Porphyria or hypersensitivity to porphyrins; 5. An active second primary cancer, defined as one with a disease-free interval of <5 years before screening, with the exception of 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); 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, with the exception of 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. Significant hearing impairment; 17. Plans to have, or has recently had, vaccination with a live vaccine, including for yellow fever; 18. Concurrently receiving treatment with phenytoin; 19. 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 ovulation12 (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. 20. Breastfeeding women or women with a positive pregnancy test at baseline; 21. Inadequate bone marrow function as evidenced by one of the following: - Absolute neutrophil count (ANC) <1.5 × 109/L - Platelet count <100 × 109/L - Haemoglobin <6 mmol/L (transfusion allowed); 22. Inadequate liver function despite satisfactory endoscopic or percutaneous biliary tree stenting, defined as: - Serum (total) bilirubin persisting at >2.5 × the ULN for the institution - AST or ALT >3.0 × ULN (>5 × ULN if liver metastases are present) - ALP levels >5.0 × ULN; 23. Inadequate renal function, as determined by local practice for patients on fractionated platinum-based chemotherapy. Patients with creatinine clearance <60 mL/min must not be included. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 (using the smallest measurements recorded since the treatment started as reference for progressive disease). Objective Response Rate: The ORR is calculated as the proportion of patients with measurable disease at baseline 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 the first documented 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
Finland |
France |
Germany |
Italy |
Korea, Republic of |
Norway |
Poland |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |