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CholangiocarcinomaPhase 2RELEASENCT04099888

PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer

A Phase 2 study testing Fimaporfin and Gemcitabine and Gemcitabine/Cisplatin chemotherapy in people with Cholangiocarcinoma, run by PCI Biotech AS at 50 sites in 14 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will assess the safety and effectiveness of fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable cholangiocarcinoma (CCA). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangiocarcinoma
What is being tested?
Fimaporfin and Gemcitabine and Gemcitabine/Cisplatin chemotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
50 sitesin 14 countries
Study dates
23 May 2019to 6 May 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each patient must provide signed and witnessed written informed consent and agree to comply with study protocol requirements.
  • Histopathologically/cytologically verified adenocarcinoma consistent with cholangiocarcinoma (CCA). Must have biliary lesion causing bile obstruction that requires stenting and is accessible for PCI light treatment (ie, extrahepatic CCA [perihilar or distal] only).
  • CCA must be considered inoperable with respect to radical resection.
  • At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation.
  • If metastatic, metastases must be limited tissues other than bone or the central nervous system.
  • Must have 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).
  • Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Estimated life expectancy of at least 12 weeks.

Who cannot join

  • Patients who have previously received any anti-tumor (either local or systemic) treatment for CCA, except for previous treatment of up to 2 cycles of gemcitabine/cisplatin.
  • Patients with severe visceral disease other than CCA.
  • A history of frequently recurring septic biliary events.
  • Patients with porphyria or hypersensitivity to porphyrins.
  • Patients with 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.
  • Patients not able to undergo contrast-enhanced CT or MRI.
Show all 23Show fewer
  • Patients currently participating in any other interventional clinical trial.
  • Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment.
  • Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment.
  • Clinically significant and uncontrolled cardiac disease except for extra systoles or minor conduction abnormalities and controlled and well-treated chronic atrial fibrillation.
  • Known allergy or sensitivity to photosensitisers (active substance and/or any of the excipients); or chronic use of other photosensitising therapies; treatment with amiodarone during the last 12 months.
  • Known hypersensitivity to or contraindication to the use of gemcitabine (active substance and/or any of the excipients).
  • Known hypersensitivity to or contraindication to the use of cisplatin (active substance and/or any of the excipients).
  • Patients with ataxia telangiectasia.
  • 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.
  • Patients planning to have or who have recently had vaccination with a live vaccine.
  • Patients concurrently receiving treatment with phenytoin.
  • Male patients unwilling to use highly effective contraception or female patients of childbearing potential unwilling to use highly effective form of contraception. Patients must continue the use of contraception during PCI treatment and subsequent chemotherapy for at least 6 months thereafter.
  • Women who are breastfeeding or who have a positive pregnancy test at baseline.
  • Patients with inadequate bone marrow function (absolute neutrophil count <1.5 x 10^9/L; platelet count <100 x 10^9/L; haemoglobin <6 mmol/L [transfusion allowed]).
  • Inadequate liver function despite satisfactory drainage (serum bilirubin persisting at >5 x upper limit of normal for the institution; aspartate aminotransferase or alanine aminotransferase >3.0 x upper limit of normal or >5 x upper limit of normal if liver metastases are present; alkaline phosphatase levels >5.0 x upper limit of normal).
  • Inadequate renal function, as determined by local practice for patients on fractionated platinum-based chemotherapy. Patients with creatinine clearance <45 mL/min (in France: <60 mL/min) must not be included.
  • Other protocol-defined criteria may apply.

Trial locations and contacts

50 sites in 14 countries.

50 sites in 14 countries

Germany11 sites

  • Universitätsklinikum Bonn

    Bonn, 53105

  • Universitätsklinikum Essen

    Essen, North Rhine-Westphalia, 45122

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, Hesse, 60590

  • Universitätsklinikum Hamburg Eppendorf, I. Medizinische Klinik und Poliklinik (Gastroenterologie mit Sektionen Infektiologie und Tropenmediz)

    Hamburg, 20246

  • Klinikum Landshut

    Landshut, 84034

  • LAKUMED Kliniken

    Landshut, 84036

  • Universität Leipzig KöR

    Leipzig, 04103

  • Klinikum Mannheim Universitätsklinikum gGmbH

    Mannheim, 68167

  • Klinikum rechts der Isar der Technischen Universität München

    München, Bavaria, 81675

  • Klinikum der Ludwig-Maximilians-Universität MünchenKlinik

    München, 81377

  • Klinikum Nürnberg Nord, Medizinische Klinik 6 - (Schwerpunkte Gastroenterologie, Hepatologie, Endokrinologie)

    Nuremberg, 90419

Other trials in Germany

United States6 sites

  • Emory University Hospital, 1365C Clifton Road NE

    Atlanta, Georgia, 30322

  • University of Chicago Medical Center, 5841 South Maryland Avenue

    Chicago, Illinois, 60637

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Baylor College of Medicine

    Houston, Texas, 77096

  • University of Louisville

    Louisville, Kentucky, 40202

  • The Mayo Clinic Hospital - Saint Mary's Campus, 1216 Second Street Southwest

    Rochester, Minnesota, 55902

Other trials in United States

South Korea6 sites

  • Pusan National University Hospital, 179 Gudeok-ro, Seo-gu

    Busan, 49241

  • Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu

    Daegu, 41404

  • National Cancer Center, 323 Ilsan-ro, Ilsandong-gu

    Goyang-si, Gyeonggido, 10408

  • Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu

    Seoul, 05505

  • Severance Hospital Yonsei University Health System, 50-1, Yonsei-Ro, Seodaemun-Gu

    Soeul, 03722

  • The Catholic University of Korea, Seoul St. Mary's Hospital, 222 Banpo-Daero Seocho-gu

    Soeul, 06591

Other trials in South Korea

Spain6 sites

  • Hospital del Mar

    Barcelona, 08033

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario HM Sanchinarro - CIOCC

    Madrid, 28050

  • Hospital Universitario Puerta de Hierro - Majadahonda

    Majadahonda, 28222

  • Clinica Universidad Navarra

    Pamplona, Navarre, 31008

  • Corporacio Sanitaria Parc Tauli

    Sabadell, 08208

Other trials in Spain

France4 sites

  • CHU Angers

    Angers, Cedex 9, 49933

  • Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon

    Grenoble, Cedex 09, 38043

  • CHU Dupuytren, 2 Avenue Martin Luther King

    Limoges, 87042

  • Institut Gustave Roussy, Département de gastro-entérologie

    Villejuif, 94805

Other trials in France

Ukraine4 sites

  • MNPE of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection

    Kharkiv

  • SI Institute for General and Urgent Surgery n.a. V.T. Zaitseva of NAMS of Uktraine

    Kharkiv

  • SI "National Institute of Surgery and Transplantology n.a. O.O. Shalimov " of NAMS of Ukraine

    Kyiv

  • Municipal Nonprofit Enterprise City Hospital #3 of Zaporizhzhia City Council

    Zaporizhzhya

Other trials in Ukraine

Taiwan3 sites

  • Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard, Sec. 4

    Taichung, 40705

  • Taipei Veterans General Hospital, No. 201, Sction 2, Shi-pai Road

    Taipei, 11217

  • Chang Gung Memorial Hospital, Linkou, Dept. of Medical Oncology, 5 Fuxing Street, Guishan

    Taoyuan, 33305

Other trials in Taiwan

Belgium2 sites

  • UZ Gent

    Ghent, Oost-Vlaanderen, 9000

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

Italy2 sites

  • IRCCS Saverio de Bellis, Via Turi, 27

    Castellana Grotte, 70013

  • Azienda Ospedaliero Universitaria Di Modena Policlinico

    Modena, Emilia-Romagna, 41100

Other trials in Italy

Poland2 sites

  • Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii

    Olsztyn, Warmian-Masurian Voivodeship, 10-228

  • Med-Polonia Sp. z o.o.

    Poznan, 60-569

Other trials in Poland

Denmark1 site

  • Odense Universitetshospital

    Odense, 5000

Other trials in Denmark

Finland1 site

  • Tampereen yliopistollinen sairaala, Syöpätautien klinikka

    Tampere, FI-33520

Other trials in Finland

Norway1 site

  • Oslo Universitetssykehus HF Radiumhospitalet

    Oslo

Other trials in Norway

Sweden1 site

  • Karolinska Universitetssjukhuset Solna, P.O Bäckencancer, Karolinska Universitetssjukhuset

    Stockholm, Stockholms Ian, SE-17176

Other trials in Sweden

About this study

Official title: A Multi-Center Randomised Open-Label Phase 2 Study to Assess the Safety, Tolerability and Efficacy of Fimaporfin-Induced Photochemical Internalisation of Gemcitabine Complemented by Gemcitabine/Cisplatin Chemotherapy Versus Gemcitabine/Cisplatin Alone in Patients With Inoperable Cholangiocarcinoma

This study will assess the safety and effectiveness of fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable cholangiocarcinoma (CCA). Participants will be randomly assigned to one of the treatment groups and will receive study treatment for 6 months, followed by assessments every 3 months, as applicable.

Read the detailed description

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma arising from cells lining the bile ducts. Standard treatment options for CCA include surgery, radiotherapy and chemotherapy, dependent upon if the CCA is intra- or extra-hepatic. Surgical removal of the tumor is the only potential cure, and CCA is very resistant to standard pharmaceutical drug treatment, though chemotherapy has some effect. Current chemotherapy uses cisplatin plus gemcitabine. Photochemical internalisation (PCI) is a novel technology, where photochemical reactions are used to enhance the effect of drugs by increasing their ability cross cell membranes to interact with their intended target. This study will assess the safety and effectiveness of fimaporfin-induced PCI of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable CCA.

NOTE: Participants are no longer being recruited to this study.

Being tested
Fimaporfin and Gemcitabine, Gemcitabine/Cisplatin chemotherapy
Keywords
Phase II, Safety, Tolerability, Efficacy, Amphinex-induced Photochemical Internalisation, PCI, Amphinex, Gemcitabine, Cisplatin, Inoperable, CCA, Cholangiocarcinoma, Bile duct cancer, Photodynamic therapy, Extrahepatic, Perihilar, Distal, Fimaporfin, Pivotal, RELEASE
Medical subject headings
Cholangiocarcinoma, Bile Duct Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fimaporfin and GemcitabineDrug

    Also called PCI treatment

    PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given.

  • Gemcitabine/Cisplatin chemotherapyDrug

    Also called Standard of care (SoC)

    Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.

Study groups in NCT04099888
Study groupRoleWhat they receive
PCI treatment in conjunction with Standard of Care (SoC)ExperimentalArm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy
Receives: Drug: Fimaporfin and Gemcitabine; Drug: Gemcitabine/Cisplatin chemotherapy
Standard of Care (SoC)Active comparatorArm B: Gemcitabine/cisplatin chemotherapy
Receives: Drug: Gemcitabine/Cisplatin chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    From date of randomisation to date of objective disease progression or death, whichever comes first (in months)

    Measured: Up to 18 months

Secondary outcomes (12)

  1. Overall Survival (OS)

    From date of randomisation to date of death from any cause (in months)

    Measured: Up to 24 months

  2. Best Overall Response (BOR)

    Best response recorded from start of treatment until disease progression/recurrence (according to RECIST 1.1)

    Measured: Up to 18 months

  3. Objective Response Rate (ORR)

    Proportion of patients with measurable disease at baseline who have at least one visit response with a complete response (CR) or partial response (PR) noted (according to RECIST 1.1)

    Measured: Up to 18 months

  4. Duration of Response (DoR)

    From first documented tumour response until first documented disease progression, or death in the absence of disease progression (in months)

    Measured: Up to 24 months

  5. Overall Disease Control Rate (DCR)

    Proportion of patients with BOR of CR, PR or stable disease (SD) (according to RECIST 1.1) at or after the first follow-up scan, partial response or complete response

    Measured: 6 months and 12 months

  6. Change in Tumor Size

    Best overall percentage change in tumour size from baseline

    Measured: Up to 18 months

  7. Loco-regional Tumour-related Events and Biliary Complications

    Frequency and severity of loco-regional tumour related events and biliary complications

    Measured: Up to 12 months

  8. Adverse Events (AEs)/Serious Adverse Events (SAEs)

    Number and proportion of patients with AEs/SAEs

    Measured: Up to 12 months

  9. Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A.

    A non-compartmental analysis (NCA) was applied on the data. AUC from time zero to the last measured concentration (AUC 0-t) was initially estimated by the linear trapezoidal method.

    Measured: Time Frame AUC calculated from time zero to C5-D8 (3 months from the first PCI treatment)

  10. Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A.

    A non-compartmental analysis (NCA) was applied on the data.

    Measured: Timepoints for pharmacokinetic (PK) sampling: Day -4 (before, 30m and 4hrs after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30m and 4hrs after Amphinex), C5-D1, and C5-D8

  11. Time to Cmax (Tmax) Was Performed for Patients in Arm A.

    A non-compartmental analysis (NCA) was applied on the data as described by Gabrielsson \& Weiner (Methods in molecular biology, 929:161-180, 2012).

    Measured: Timepoints for PK sampling: Day -4 (before, 30 min and 4 hours after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30 min and 4 hours after Amphinex) , C5-D1, and C5-D8

  12. Health-related Quality of Life (QoL)

    QoL assessment. Patients select one of four answers to 22 questions ranging from 1 (not at all) to 4 (very much). Lower total scores indicate a more favorable QoL perception than a higher score.

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2019
  2. Study start23 May 2019
  3. Primary completion28 Apr 2022
  4. Study completion6 May 2022

Why it stopped: Recent results from a Phase 3 study are expected to change the standard of care for patients with inoperable CCA, rendering the RELEASE study challenging to complete and potentially inadequate for NDA approval.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04099888
Sponsor's protocol ID
PCIA 203/18
Acronym
RELEASE
Status last verified
Apr 2023
First submitted
26 Jul 2019
Last updated
11 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fimaporfin and Gemcitabine and Gemcitabine/Cisplatin chemotherapy in people with Cholangiocarcinoma, run by PCI Biotech AS at 50 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in Germany, United States, South Korea, Spain, France and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04099888.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2023.

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