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

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ClinicalTrials.gov Identifier: NCT04099888
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
PCI Biotech AS

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.

Condition or disease Intervention/treatment Phase
Cholangiocarcinoma Drug: Fimaporfin and Gemcitabine Drug: Gemcitabine/Cisplatin chemotherapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 186 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 23, 2019
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : April 2024


Arm Intervention/treatment
Experimental: PCI treatment in conjunction with Standard of Care (SoC)
Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy
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/m²) 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)

Active Comparator: Standard of Care (SoC)
Arm B: Gemcitabine/cisplatin chemotherapy
Drug: Gemcitabine/Cisplatin chemotherapy
Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Other Name: Standard of care (SoC)




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to 24 months ]
    From date of randomisation to date of death from any cause (in months)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. Change in tumor size [ Time Frame: Up to 18 months ]
    Best overall percentage change in tumour size from baseline (in millimeters (mm))

  7. 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

  8. Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months ]
    Number and proportion of patients with AEs/SAEs

  9. Area under the plasma concentration curve (AUC) [ Time Frame: Up to 12 months ]
    In Arm A patients

  10. Maximum observed concentration (Cmax) [ Time Frame: Up to 12 months ]
    In Arm A patients

  11. Time to Cmax (Tmax) [ Time Frame: Up to 12 months ]
    In Arm A patients

  12. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Each patient must provide signed and witnessed written informed consent and agree to comply with study protocol requirements.
  2. 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).
  3. CCA must be considered inoperable with respect to radical resection.
  4. At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation.
  5. If metastatic, metastases must be limited tissues other than bone or the central nervous sytem.
  6. 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).
  7. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  8. Estimated life expectancy of at least 12 weeks.

Exclusion Criteria:

  1. 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.
  2. Patients with severe visceral disease other than CCA.
  3. A history of frequently recurring septic biliary events.
  4. Patients with porphyria or hypersensitivity to porphyrins.
  5. 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.
  6. Patients not able to undergo contrast-enhanced CT or MRI.
  7. Patients currently participating in any other interventional clinical trial.
  8. Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment.
  9. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment.
  10. Clinically significant and uncontrolled cardiac disease except for extra systoles or minor conduction abnormalities and controlled and well-treated chronic atrial fibrillation.
  11. 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.
  12. Known hypersensitivity to or contraindication to the use of gemcitabine (active substance and/or any of the excipients).
  13. Known hypersensitivity to or contraindication to the use of cisplatin (active substance and/or any of the excipients).
  14. Patients with ataxia telangiectasia.
  15. 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.
  16. Patients planning to have or who have recently had vaccination with a live vaccine.
  17. Patients concurrently receiving treatment with phenytoin.
  18. 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.
  19. Women who are breastfeeding or who have a positive pregnancy test at baseline.
  20. 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]).
  21. 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).
  22. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04099888


Locations
Show Show 47 study locations
Sponsors and Collaborators
PCI Biotech AS
Investigators
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Study Director: PCI Biotech PCI Biotech
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Responsible Party: PCI Biotech AS
ClinicalTrials.gov Identifier: NCT04099888    
Other Study ID Numbers: PCIA 203/18
First Posted: September 23, 2019    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PCI Biotech AS:
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
PDT
FimaChem
Klatskin
Additional relevant MeSH terms:
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Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs