A study to investigate the safety, tolerability and efficacy of PCI/Gemcitabine treatment followed by combination chemotherapy in patients with cholangiocarcinomas

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2012-002888-10-LT
• Date of registration: 08/06/2015
• Prospective Registration: Yes
• Primary sponsor: PCI Biotech AS
• Public title: A study to investigate the safety, tolerability and efficacy of PCI/Gemcitabine treatment followed by combination chemotherapy in patients with cholangiocarcinomas
• Scientific title: A Phase I/II Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of AmphinexTM-induced Photochemical Internalisation (PCI) of Gemcitabine followed by Gemcitabine/Cisplatin Chemotherapy in Patients with Advanced Inoperable Cholangiocarcinomas
• Date of first enrolment: 30/09/2015
• Target sample size: 61
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002888-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: PCI procedure + combination chemotherapy vs combination chemotherapy alone; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, France, Germany, Lithuania, Norway, United Kingdom

Contacts

• Name: Regulatory Affairs
• Affiliation: Theradex (Europe) Ltd

• Name: Regulatory Affairs
• Affiliation: Theradex (Europe) Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histopathologically/cytologically (C5) verified adenocarcinoma consistent with cholangiocarcinoma.
2. Cholangiocarcinoma that:
- Is considered to be inoperable
- Is a primary lesion in the perihilar biliary duct region that requires stent placement
- Has nodal enlargement = to N1 as per CT/MRI assessment
- 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. Performance status ECOG = 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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

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 < 5 years before registration/randomization.
7. Inability to undergo CT or MRI.
8. Current participation in any other interventional clinical trial.
9. Male patients not willing to use adequate contraception or female patients of childbearing potential not willing to use an effective form of contraception such as hormonal birth control, intrauterine device or double barrier method during PCI treatment and subsequent chemotherapy and for at least 6 months thereafter.
10. Breast feeding women or women with a positive pregnancy test at baseline.
11. Inadequate bone marrow function:
- Absolute Neutrophil Count (ANC): < 1.5 x 109/L, or platelet count < 100 x 109/L or haemoglobin <6 mmol/L (transfusion allowed).
12. Inadequate liver function, defined as:
- Serum (total) bilirubin > 2.5 x the Upper Limit of Normal (ULN) for the institution.
- Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3.0 x ULN (> 5 x ULN if liver metastases are present)
- Alkaline phosphatase (ALP) levels > 5.0 x ULN.
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 six 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)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Inoperable advanced cholangiocarcinomas
MedDRA version: 19.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Amphinex
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Amphiporfin
CAS Number: 1265603-15-3
Current Sponsor code: TPCS2a.2MEA
Other descriptive name: Di (monoethanolammonium) meso-tetraphenyl chlorin disulphonate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4

Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CISPLATIN
CAS Number: 15663-27-1

Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4

Primary Outcome(s)

Main Objective: The phase I primary objective is 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 CCA.

The phase II primary objective is 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 CCA.

Secondary Objective: The Phase I secondary objectives are:
• To characterize the pharmacokinetic (PK) 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 CCA.

The Phase II secondary objectives are:
• To characterize the PK profiles of Amphinex® and gemcitabine in a limited number of patients.
• To further assess the safety profile of Amphinex®-induced PCI of gemcitabine followed by the systemic gemcitabine/cisplatin combination.

Timepoint(s) of evaluation of this end point: DLT - from start of treatment up to the end of cycle 1 of combination chemotherapy for dose escalation patients only.

Safety profile - AEs/laboratory sampling from time of consent up to 30 days after the last administration of systemic chemotherapy. Physical examinations continue every 3 months for phase II patients (and phase I patients at the dose level selected for phase II) without disease progression or study discontinuation for any reason for up to 15 months after the end of treatment visit.

PFS - calculated from randomisation to documented disease progression (according to modified RECIST 1.1 criteria) or death from any cause.

Primary end point(s): Phase I (safety)
• Dose-limiting toxicities (DLT) and the safety profile (AEs, laboratory assessments and physical findings) of the Amphinex®-induced PCI of gemcitabine followed by the gemcitabine/cisplatin combination.

Phase II (efficacy)
• Progression Free Survival (PFS), defined as the time from randomization to documented disease progression (according to RECIST 1.1 criteria) or death from any cause.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: PK Amphinex - pre-dose sample and 4 post-doing samples over 24 hours, further samples at 6 days after dosing, 6 weeks after dosing and 3 months after dosing
PK Gemcitabine - pre-dose sample and 8 post-dosing samples over 24 hours.

PFS - calculated from randomisation to documented disease progression or death from any cause.
ORR and DCR - post-treatment CT/MRI scans 3 months and 6 months after start of combination chemotherapy, then every 3 months until PD or death.
OS - from randomisation to the date of death from any cause.

Safety profile - AEs/laboratory sampling from time of consent up to 30 days after the last administration of systemic chemotherapy. Physical exam continue every 3 months for patients without disease progression for up to 15 months after the off-study visit.

Secondary end point(s): Phase I
- PK profile of Amphinex and gemcitabine in plasma.
- PFS, defined as the time from registration to documented disease progression (according to RECIST 1.1 criteria) or death from any cause.
- Best Overall Response (BOR)

Phase II
- Overall Response Rate (ORR), calculated as the proportion of patients with a BOR of confirmed Complete Response (CR) or Partial Response (PR).
- Disease Control Rate (DCR), defined as the proportion of patients with BOR of confirmed CR, PR or Stable Disease (SD).
- Overall Survival (OS), calculated as the time from randomization to the date of death from any cause.
- BOR
- PK profile of Amphinex in bile
- Safety profile (AEs, laboratory assessments and physical findings) of the Amphinex-induced PCI of gemcitabine followed by the gemcitabine/cisplatin combination, or the gemcitabine/cisplatin combination alone.

Secondary ID(s)

PCIA202/12

2012-002888-10-GB

Source(s) of Monetary Support

PCI Biotech AS

Ethics review

Status: Approved
Approval date:
Contact: