Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by PCI Biotech AS
Information provided by (Responsible Party):
PCI Biotech AS Identifier:
First received: May 15, 2013
Last updated: October 12, 2016
Last verified: October 2016
This is a Phase I/II 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.

Condition Intervention Phase
Drug: Amphinex and Gemcitabine
Drug: Gemcitabine and Cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of PCI of Gemcitabine Followed by Gemcitabine/Cisplatin Chemotherapy in Patients With Inoperable Cholangiocarcinomas

Resource links provided by NLM:

Further study details as provided by PCI Biotech AS:

Primary Outcome Measures:
  • Determine a safe and tolerable dose (Phase I) [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]
    Dose-limiting toxicities (DLT) and the safety profile

  • Preliminary assessment of efficacy (Phase II) [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    Progression Free Survival (PFS)- from registration to progression

Secondary Outcome Measures:
  • Best Overall Response (BOR) [ Time Frame: Up to 15 months. ] [ Designated as safety issue: No ]
    Number and proportion of patients with CR, PR, SD PD and NE

  • Pharmacokinetics (PK) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Pharmacokinetics profile of Amphinex and Gemcitabine in Plasma

  • Disease Control Rate (DCR) [ Time Frame: up to 15 months ] [ Designated as safety issue: No ]
    Proportion of patients with best overall response of CR, PR or SD

  • Overall Response Rate (ORR) [ Time Frame: up to 15 months ] [ Designated as safety issue: No ]
    Proportion of patients with best overall response rate of CR and PR

  • Overall Survival (OS) [ Time Frame: up to 15 months ] [ Designated as safety issue: No ]
    Time from randomization to death

  • Safety Profile (Phase II) [ Time Frame: up to 15 months ] [ Designated as safety issue: Yes ]
    AEs, Laboratory assessments and physical findings

  • Progression Free Survival (PFS) (Phase I) [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    time from registration to documented disease progression or death

Other Outcome Measures:
  • Time to re-intervention (Exploratory Endpoint) [ Time Frame: Up to 15 months ] [ Designated as safety issue: Yes ]
    stent patency

  • Skin photosensitivity (Exploratory Endpoint) [ Time Frame: Up to 1 month ] [ Designated as safety issue: Yes ]
    Use of patient questionnaire

  • Pharmacokinetic (PK) (Exploratory Endpoint) [ Time Frame: up to 1 week ] [ Designated as safety issue: Yes ]
    Measuring the Amphinex concentration in faeces

  • Evaluation of immune modulation effects (Exploratory Endpoint) [ Time Frame: up to 15 months ] [ Designated as safety issue: No ]
  • Biomarkers (Exploratory Endpoint) [ Time Frame: up to 15 months ] [ Designated as safety issue: No ]
    Measuring potential early prediction of response and disease progression in blood and bile samples

  • Local tumor response [ Time Frame: up to 15 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: May 2013
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amphinex and Gemcitabine
Arm A Phase II: Stented patients. Amphinex administration on day 0, followed by gemcitabine administration (1000 mg/m2) intravenously over 30 minutes 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, commencing between 7 and 21 days after the laser light application
Drug: Amphinex and Gemcitabine
Amphinex administration on day 0, followed by gemcitabine administration (1000 mg/m2) intravenously over 30 minutes 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, commencing between 7 and 21 days after the laser light application.
Other Names:
  • Gemzar (Gemcitabine)
  • Fimaporfin (Amphinex)
Active Comparator: Gemcitabine and Cisplatin
Arm B Phase II: Stented patients. Systemic gemcitabine (1000 mg/m2) intravenously over 30 minutes and cisplatin intravenously over a period of 1 hour (25 mg/m2) given on Day 1 and Day 8 of each 21-day cycle, commencing within 21 days after randomization.
Drug: Gemcitabine and Cisplatin
No PCI treatment (stenting only) followed by systemic gemcitabine (1000 mg/m2) intravenously over 30 minutes and cisplatin intravenously over a period of 1 hour (25 mg/m2) given on Day 1 and Day 8 of each 21-day cycle, commencing between 7 and 21 days after randomization.
Other Names:
  • Gemzar
  • Cisplatin

Detailed Description:

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma arising from the neoplastic transformation of cholangiocytes, the epithelial cells lining the intra-hepatic and extra-hepatic bile ducts. CCA accounts for about 3% of all digestive tumours and 10-15% of the hepatobiliary tumours. It has an annual incidence of 1-2 cases per 100,000 in the Western World, but rates of CCA have been steadily rising worldwide over the past several decades. On a global scale, CCA is the second most common primary hepatic malignancy These tumours have a poor overall survival with a 5-year survival of about 5%. Over 50% of patients present with advanced-stage disease, and the prognosis is poor with the survival of between 6-12 months for unresected patients, even after biliary decompression. CCA may arise anywhere in the biliary tree, from the small, peripheral hepatic ducts to the distal common bile duct. Commonly used classification systems utilise anatomical location to group tumours into three main categories: intra-hepatic (20-25%), perihilar (also known as Klatskin tumour - 50%) and distal (20-25%).

Hilar CCA is an adenocarcinoma of the extrahepatic biliary tree arising from the main left or right hepatic ducts or their confluence. There has a been a growing recognition that hilar CCA disease actually has a distinct biological behaviour and natural history compared to that of (distal) extra-hepatic CCA, and increasing acknowledgment that different therapeutic strategies are required (10). At initial presentation of patients with extra-hepatic CCA, 30-50% will have local lymph node involvement and 10-20% metastatic spread typically to the liver and peritoneum. With hilar CCA due to the long asymptomatic course, only 20% are resectable at time of diagnosis.

Standard treatment options for CCA include surgery, radiotherapy and chemotherapy, dependent upon if the CCA is intra- or extra-hepatic. Tumour resection is the only potential cure for CCA. Recent advances in transplantation using stringent selection criteria and utilization of neoadjuvant chemoradiation have demonstrated encouraging results with 5 year survival rates of over 70%, with even one series from The Mayo Clinic yielding a 5-year survival rate of 82%. For the 80% who present with unresectable disease, the utility of these modalities combined with biliary decompression interventions only provided a median survival time of 3-6 months from the time of diagnosis.

For these patients with inoperable locally advanced CCA the main treatment aim is palliative to relieve local symptoms such as pain and jaundice. Surgery for these patients is primarily for creating a bypass in patients who cannot be stented. CCA is remarkably resistant to pharmacological therapy, but activity has been seen using chemotherapy; mainly gemcitabine given either as monotherapy or paired with either a platin derivative or a fluoropyrimidine as a doublet treatment and more recently docetaxel, these give partial response rates of 0-9% and an average survival advantage of 2-12 months. Concerning biological therapy, the ongoing studies using sorafenib, lapatinib or bevacizumab have yielded some promising results, with sorafenib demonstrating therapeutic benefit in a single arm PhII study. For patients who are unsuitable for curative resection, the current systemic combination chemotherapy is with cisplatin plus gemcitabine. This was established in the largest randomized phase III study to date in non-operable biliary tract cancer which demonstrated a response rate of 81.4% and a median overall survival of 11.7 months; notably there was no statistically significant increase in toxicity when compared to gemcitabine monotherapy. The recent advances in interventional and endoscopic technology have seen a rise in highly specialized centres that are able to deliver very precise local control treatments aimed at gaining local control; these include local ablation and embolization, brachytherapy, radio-frequency ablation and, most significantly, photodynamic therapy which, with its favourable adverse-event profile, is recommended by most recent review articles for non-resectable patients.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histopathologically/cytologically (C5) verified adenocarcinoma consistent With cholangiocarcinoma
  2. 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
  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.

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 10^9/L, or platelet count < 100 x 10^9/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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01900158

Contact: Dr. Richard Sturgess, MD 0044(0)151 529 8157
Contact: Dr Dan Palmer, MD 0044 (0)151 706 4177

National Center for Tumor Diseases Active, not recruiting
Heidelberg, Baden-Württemberg, Germany, D-69120
Klinikum rechts der Isar Recruiting
Munich, Bayern, Germany, 81675
Contact: Hana Alguel, PhD   
Klinikum der Ludwig-Maximilians-Universität Recruiting
München, Bayern, Germany, 81377
Contact: Prof. Dr. Jörg Schirra, MD    +49 89 4400 73031   
Klinikum der Johann Wolfgang Goethe-Universität Recruiting
Frankfurt am Main, Hessen, Germany, 60590
Contact: Prof. Dr. Jörg Trojan, MD    +49 69 6301 87686   
Universitätsklinikum Essen Recruiting
Essen, Nordrhein-Westfalen, Germany, 45122
Contact: Stefan Kasper, MD    +49 201 723 1631   
Contact: Alexander Dechêne, MD    +49 49 201 723 2390   
Klinikum Ludwigshafen Active, not recruiting
Ludwigshafen, Rheinland-Pfalz, Germany, D-67063
Universitätsklinikum Leipzig Recruiting
Leipzig, Sachsen, Germany, 04103
Contact: Prof. Dr. Albrecht Hoffmeister, MD    + 49341 9712251   
Klinikum Augsburg Not yet recruiting
Augsburg, Germany, 86156
Contact: Helmut Messmann, MD    0049 821 400-2351   
Charité, Campus Mitte Recruiting
Berlin, Germany, D-10117
Contact: Dr. med. Christian Jürgensen, MD    0049 30 450 514 134   
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Active, not recruiting
Dresden, Germany, 01307
Hospital of Lithuanian University of Health Sciences (LUHS) Not yet recruiting
Kaunas, Lithuania, LT-50009
Contact: Limas Kupcinskas, MD    0037068640575   
National Cancer institute Not yet recruiting
Vilnius, Lithuania, LT-08660
Contact: Mantas Trakymas, MD    0037061534951   
Vilnius University hospital Santariskiu Klinikos Not yet recruiting
Vilnius, Lithuania, LT-08661
Contact: Juozas Stanaitis, MD    0037068661534   
Oslo Universtiy Hospital Active, not recruiting
Oslo, Norway, 0310
United Kingdom
University Hospital Aintree Recruiting
Aintree, Liverpool, United Kingdom, L9 7AL
Contact: Dr Richard Sturgess, MD    0044 (0) 151 529 8157   
Contact: Dr Dan Palmer, MD    0044 (0)151 706 4177   
Hammersmith Hospital Not yet recruiting
London, United Kingdom, W12OHS
Contact: Christopher Wadsworth         
Sponsors and Collaborators
PCI Biotech AS
Principal Investigator: Dr Richard Sturgess, MD University Hospital Aintree
  More Information

Additional Information:
Responsible Party: PCI Biotech AS Identifier: NCT01900158     History of Changes
Other Study ID Numbers: PCI A202/12  2012-002888-10 
Study First Received: May 15, 2013
Last Updated: October 12, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Norway: Norwegian Medicines Agency
Lithuania: State Medicine Control Agency - Ministry of Health
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by PCI Biotech AS:
Phase I, Phase II, Dose Escalation, Safety, Tolerability,
Efficacy, Amphinex induced Photochemical Internalisation, PCI, Amphinex, Gemcitabine, Cisplatin,
Inoperable Cholangiocarcinomas, CCA, Cholangiocarcinoma, bile duct cancer, photodynamic therapy

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on October 27, 2016