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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04099888
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : October 9, 2020
Sponsor:
Information provided by (Responsible Party):
PCI Biotech AS

Tracking Information
First Submitted Date  ICMJE July 26, 2019
First Posted Date  ICMJE September 23, 2019
Last Update Posted Date October 9, 2020
Actual Study Start Date  ICMJE May 23, 2019
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2019)
Progression-free survival (PFS) [ Time Frame: Up to 18 months ]
From date of randomisation to date of objective disease progression or death, whichever comes first (in months)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2019)
  • Overall survival (OS) [ Time Frame: Up to 24 months ]
    From date of randomisation to date of death from any cause (in months)
  • Best Overall Response (BOR) [ Time Frame: Up to 18 months ]
    Best response recorded from start of treatment until disease progression/recurrence (according to RECIST 1.1)
  • Objective Response Rate (ORR) [ Time Frame: Up to 18 months ]
    Proportion of patients with measurable disease at baseline who have at least one visit response with a CR (complete response) or PR (partial response) noted (according to RECIST 1.1)
  • Duration of Response (DoR) [ Time Frame: Up to 24 months ]
    From first documented tumour response until first documented disease progression, or death in the absence of disease progression (in months)
  • Disease Control Rate (DCR) [ Time Frame: At 6 months and 12 months ]
    Proportion of patients with BOR of CR, PR or SD (stable disease) (according to RECIST 1.1)
  • Change in tumor size [ Time Frame: Up to 18 months ]
    Best overall percentage change in tumour size from baseline (in millimeters (mm))
  • Loco-regional tumour-related events and biliary complications [ Time Frame: Up to 12 months ]
    Frequency and severity of loco-regional tumour related events and biliary complications
  • Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months ]
    Number and proportion of patients with AEs/SAEs
  • Area under the plasma concentration curve (AUC) [ Time Frame: Up to 12 months ]
    In Arm A patients
  • Maximum observed concentration (Cmax) [ Time Frame: Up to 12 months ]
    In Arm A patients
  • Time to Cmax (Tmax) [ Time Frame: Up to 12 months ]
    In Arm A patients
  • Health-related Quality of Life (QoL) [ Time Frame: Up to 18 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer
Official Title  ICMJE 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
Brief 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). 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cholangiocarcinoma
Intervention  ICMJE
  • Drug: Fimaporfin and Gemcitabine
    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/m^2) and intraluminal laser light application. Up to 2 PCI treatments will be given.
    Other Name: PCI treatment
  • Drug: Gemcitabine/Cisplatin chemotherapy
    Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
    Other Name: Standard of care (SoC)
Study Arms  ICMJE
  • Experimental: PCI treatment in conjunction with Standard of Care (SoC)
    Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy
    Interventions:
    • Drug: Fimaporfin and Gemcitabine
    • Drug: Gemcitabine/Cisplatin chemotherapy
  • Active Comparator: Standard of Care (SoC)
    Arm B: Gemcitabine/cisplatin chemotherapy
    Intervention: Drug: Gemcitabine/Cisplatin chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 20, 2019)
186
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2024
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Each patient must provide signed and witnessed written informed consent and agree to comply with study protocol requirements.
  • Histopathologically/cytologically (C5) verified adenocarcinoma consistent with cholangiocarcinoma (CCA).
  • CCA must be considered inoperable with respect to radical resection.
  • CCA must present with at least 1 lesion (measurable and/or non-measurable but evaluable) that can be accurately assessed at baseline and is suitable for repeated evaluation.
  • If metastatic, metastases must be limited to liver parenchyma only and/or restricted only to the local lymph nodes with peritoneal engagement locally within close proximity to the hepatoduodenal ligament.
  • Must have biliary lesion causing bile obstruction that requires stenting and is accessible for PCI light treatment (ie, extrahepatic CCA [perihilar or distal] only).
  • Must have 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).
  • Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Estimated life expectancy of at least 12 weeks.

Exclusion Criteria:

  • Patients who have previously received any anti-tumor (either local or systemic) treatment for CCA.
  • Patients with severe visceral disease other than CCA.
  • Patients with primary sclerosing cholangitis.
  • Patients with porphyria or hypersensitivity to porphyrins.
  • Patients with 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).
  • Patients not able to undergo contrast-enhanced CT or MRI.
  • 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 with the exception of 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.
  • 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.
  • Patients with significant hearing impairment.
  • 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 endoscopic or percutaneous biliary tree stenting (serum bilirubin persisting at >2.5 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: If sites have contact information, please contact directly. If not please email ClinicalTrials@pcibiotech.com
Contact: First line of the email MUST contain NCT# and Site Name
Listed Location Countries  ICMJE Belgium,   Denmark,   Finland,   France,   Germany,   Italy,   Korea, Republic of,   Norway,   Poland,   Spain,   Sweden,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04099888
Other Study ID Numbers  ICMJE PCIA 203/18
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PCI Biotech AS
Study Sponsor  ICMJE PCI Biotech AS
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: PCI Biotech PCI Biotech
PRS Account PCI Biotech AS
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP