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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 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,
Sponsor: PCI Biotech AS

Current Primary Outcome:

  • Determine a safe and tolerable dose (Phase I) [ Time Frame: up to 6 months ]
    Dose-limiting toxicities (DLT) and the safety profile
  • Preliminary assessment of efficacy (Phase II) [ Time Frame: Up to 15 months ]
    Progression Free Survival (PFS)- from registration to progression


Original Primary Outcome:

  • Dose limiting Toxicity - Phase I (safety) [ Time Frame: up to 9 months ]
    Dose-limiting toxicities (DLT) and the safety profile
  • Efficacy- Phase II (efficacy) [ Time Frame: Up to 17 months ]
    Progression Free Survival (PFS)


Current Secondary Outcome:

  • Best Overall Response (BOR) [ Time Frame: Up to 15 months. ]
    Number and proportion of patients with CR, PR, SD PD and NE
  • Pharmacokinetics (PK) [ Time Frame: 3 months ]
    Pharmacokinetics profile of Amphinex and Gemcitabine in Plasma
  • Disease Control Rate (DCR) [ Time Frame: up to 15 months ]
    Proportion of patients with best overall response of CR, PR or SD
  • Overall Response Rate (ORR) [ Time Frame: up to 15 months ]
    Proportion of patients with best overall response rate of CR and PR
  • Overall Survival (OS) [ Time Frame: up to 15 months ]
    Time from randomization to death
  • Safety Profile (Phase II) [ Time Frame: up to 15 months ]
    AEs, Laboratory assessments and physical findings
  • Progression Free Survival (PFS) (Phase I) [ Time Frame: up to 6 months ]
    time from registration to documented disease progression or death


Original Secondary Outcome:

  • Best Overall Response [ Time Frame: Up to 24 months. ]
    Number and proportion of patients with CR, PR, SD PD and NE
  • Pharmacokinetics [ Time Frame: 3 months ]
    Pharmacokinetics profine of Amphinex and Gemcitabine in Plasma
  • Disease Control Rate (DC) [ Time Frame: up to 24 months ]
    Proportion of patients with best overall response of CR, PR or SD
  • Overall Response Rate [ Time Frame: up to 24 months ]
    Proportion of patients with best overall response rate of CR and PR
  • Overall Survival [ Time Frame: up to 24 months ]
  • Safety Profile (Phase II) [ Time Frame: up to 24 months ]


Information By: PCI Biotech AS

Dates:
Date Received: May 15, 2013
Date Started: May 2013
Date Completion:
Last Updated: October 12, 2016
Last Verified: October 2016