A Phase I/II Safety and Efficacy Study of PCI of Gemcitabine and Chemotherapy in Patients With Cholangiocarcinomas

NCT01900158 | Completed Phase 1 DMC

• 2 other identifiers: PCI A202/122012-002888-10
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 11

Brief Summary

This is a Phase I Dose Escalation Study in which the safety, tolerability and efficacy of Amphinex®--induced Photochemical Internalisation (PCI) of Gemcitabine followed by Gemcitabine/Cisplatin Chemotherapy will be assessed in patients with advanced inoperable cholangiocarcinomas.

Conditions

Cholangiocarcinoma

Keywords

Phase I; CCA; Cholangiocarcinoma; bile duct cancer; klatskin; perihilar; Amphinex; Gemcitabine; Photochemical internalisation; Safety; Tolerability; Efficacy; Cisplatin; PCI; extrahepatic; local control; local tumour treatment; biliary; fimaporfin

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (DLT) and the safety profile

  Clinically significant toxicity or abnormal laboratory value assessed as unrelated to the underlying disease, criteria's based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.02: * Photosensitivity Grade 3 outside the treatment area, except for areas exposed for skin sensitivity tests and areas exposed for re-introduction to normal light. Patient compliance with light protection guidelines MUST be followed; noncompliance will be taken into account * Phototoxicity Grade 4 inside the treatment area (e.g., duodenal ulceration). * Non-haematological toxicity (excluding nausea and vomiting) ≥Grade 3. * Neutropenia or thrombocytopenia Grade 4. * All other Grade 3 toxicities that are clinically unexpected.

  up to 6 months

• Schedule-limiting toxicities (SLTs) and the safety profile

  Clinically significant toxicity or abnormal laboratory value assessed as unrelated to the underlying disease criteria's based on the NCI CTCAE version 4.02: * Photosensitivity Grade 3 outside the treatment area, except for areas exposed for skin sensitivity tests and areas exposed for re-introduction to normal light despite following prescribed precautions. Patient compliance with light protection guidelines MUST be followed; noncompliance will be taken into account * Clinically significant phototoxicity inside the treatment area (e.g., duodenal ulceration, cholangitis or pancreatitis requiring interventional radiology, operative intervention or would lead to such intervention including events that would have life-threatening consequences) * A toxicity of any grade that is clinically unexpected and considered related to the PCI treatment (changes to cisplatin treatment alone will not be included as part of this assessment).

  up to 6 months

Secondary Outcomes (3)

• Measuring the Amphinex and Gemcitabine concentration in blood plasma

  Up to 8 months

• Progression-free survival (according to RECIST 1.1 criteria)

  Up to documented disease progression or death (or Database lock)

• Best Overall Response (according to RECIST 1.1 criteria)

  Up to Database lock

Other Outcomes (4)

• Time to re-intervention (stent patency)

  Up to 8 months

• Patient questionnaire and "in clinic" evaluations

  Up to 8 months

• Measuring of Amphinex concentration in faeces

  up to 1 week after Amphinex administration

Study Arms (1)

Phase I

EXPERIMENTAL

Experimental PCI treatment in dose escalation cohorts consist of Amphinex injection (at different doses) plus a single standard dose of Gemcitabine (1000 mg/m2) plus intraluminal light at the tumour area (at different doses). In addition up to 8 cycles of standard chemotherapy doses of Gemcitabine (1000 mg/m2) and Cisplatin (25 mg/m2) was provided. In the Extended part of the study (last cohort) an additional PCI treatment was introduced at Cycle 5 in the treatment Schedule.

Drug: Amphinex, Gemcitabine and Cisplatin

Interventions

Amphinex, Gemcitabine and Cisplatin DRUG

Amphinex administration on day 0, followed by gemcitabine administration (1000 mg/m2) and laser light application (652 nm) on day 4 followed by systemic gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) given on Day 1 and Day 8 of each 21-day cycle, for up to a total of eight cycles. Either one or two PCI treatments (Amphinex, Gemcitabine and intraluminal laser light of 652nm) during the 8 cycles of chemotherapy

Also known as: Gemzar (Gemcitabine), Fimaporfin (Amphinex), Cisplatin

Phase I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically/cytologically (C5) verified adenocarcinoma consistent with cholangiocarcinoma
• Cholangiocarcinoma that:
• Is considered to be inoperable
• Has 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
• 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).
• Age ≥ 18 years.
• Performance status ECOG ≤ 1.
• Estimated life expectancy of at least 12 weeks.
• Written informed consent.

You may not qualify if:

• Any prior anti-cancer (either local or systemic) treatment for cholangiocarcinoma.
• Patients with extra-hepatic metastatic cholangiocarcinoma.
• Patients with a severe visceral disease other than cholangiocarcinoma.
• Patients with primary sclerosing cholangitis.
• Patients with porphyria or hypersensibility to porphyrins.
• 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.
• Inability to undergo CT or MRI.
• Current participation in any other interventional clinical trial.
• 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.
• Breast feeding women or women with a positive pregnancy test at baseline.
• Inadequate bone marrow function:
• Absolute Neutrophil Count (ANC): \< 1.5 x 10\^9/L, or platelet count \< 100 x 10\^9/L or haemoglobin \< 6 mmol/L (transfusion allowed).
• 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)

Sponsors & Collaborators

• PCI Biotech AS: lead

Study Sites (11)

CHU Angers

Angers, Maine-et-Loire, 49933, France

Location

Klinikum rechts der Isar, Technische Universität München

Munich, Bavaria, 81675, Germany

Location

Klinikum der Ludwig-Maximilians-Universität

München, Bavaria, 81377, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universität

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

Klinikum Ludwigshafen

Ludwigshafen am Rhein, Rhineland-Palatinate, D-67063, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Charité, Campus Mitte

Berlin, D-10117, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Oslo Universtiy Hospital

Oslo, 0310, Norway

Location

University Hospital Aintree

Aintree, Liverpool, L9 7AL, United Kingdom

Location

Related Links

• Sponsor

MeSH Terms

Conditions

Cholangiocarcinoma; Bile Duct Neoplasms

Interventions

Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Dr Richard Sturgess, MD

  University Hospital Aintree

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I Dose escalation study With 4 cohorts of different doses of light and fimaporfin (Dose Escalation) plus and additional cohort With one repeated treatment of the dose selected for one treatment (Extended).

Study Record Dates

• First Submitted: May 15, 2013
• First Posted: July 16, 2013
• Study Start: May 1, 2013
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: October 29, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8); GB (1); FR (1); NO (1)