Clinical Trial: Durvalumab(MEDI4736)/Tremelimumab in Combination With Gemcitabine/Cisplatin in Chemotherapy-naïve Biliary Tract Cancer

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

Official Title: Biomarker-oriented Study of Durvalumab(MEDI4736)/Tremelimumab in Combination With Gemcitabine/Cisplatin in Chemotherapy-naïve Biliary Tract Cancer

Brief Summary:

<Research Hypothesis> The dynamics of immune systems by cytotoxic chemotherapy and its changes by combination with immuno-oncology agents will be uncovered.

The combination of Durvalumab/Tremelimumab with gemcitabine/cisplatin chemotherapy is feasible and efficacious in chemo-naïve biliary tract cancer.

<Purpose of the study> To assess the effect of Durvalumab/Tremelimumab in combination with gemcitabine/cisplatin on response rate (RR) in chemo-naïve advanced biliary tract cancer patients.


Detailed Summary:

<Rationale for conducting this study>

  1. Rational #1. The incidence of biliary tract cancer (BTC) is higher in Korea than the West. (Korea: 10 new cases/100,000 population every year, the West:1-2 cases/100,100 population every year). Therefore, to conduct clinical study of BTC in Korea is very feasible and efficient.
  2. Rational #2 The Gemcitabine/cisplatin is the current standard of care in 1st-line treatment for advanced BTC ((N Engl J Med 2010; 362 (14): 1273-81). No one-targeted therapy has been approved in BTC, yet. The overall survival of advanced BTC with cytotoxic chemotherapy is only 8-10 months, in general. Therefore, there is a huge unmet medical need.
  3. Rational #3 In recent sequencing data of BTC showed the BTC patients with the worse prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules. According, immune-modulating therapies also be potentially promising options for these patients (Nat Genet. 2015 Sep;47(9):1003-10.)
  4. Rational #4 In PDL1 (+) BTC, anti-PD1 Ab shows promising activity as a monotherapy (Bang YJ, et al. ECC/ESMO 2015) In one clinical study of pembrolizumab, 37 out of 89 BTC patients (41.6%) showed the PDL1 (+) tumor. Among 24 PDL1 (+) patients who were enrolled and treated with pembrolizumab, 50% were Asian, 62.5% had ECOG 1, 16.7% had gallbladder cancer, 80% were at the 3rd-line or later setting. Four patients showed PR (3 from Seoul National University Hospital), 4 patients SD, which led the overall response rate of 17.4%. A total 40% of patients showed tumor shrinkage. The decreases in tumor size were generally maintained over time. This study gives us the evidence that immune checkpoint inhibitor is working on BTC likewise
    Sponsor: Seoul National University Hospital

    Current Primary Outcome: Response rate [ Time Frame: 6 weeks ]

    According to RECIST v1.1 criteria


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Disease control rate [ Time Frame: 6 weeks ]
      the percentage of patients who have achieved complete response, partial response and stable disease
    • Progression-free survival [ Time Frame: 6 weeks ]
      Time from randomization until disease progression or death
    • Duration of response [ Time Frame: 1 year ]
      Time from documentation of tumor response to disease progression
    • Overall survival [ Time Frame: 1 year ]
      Time from randomization until death from any cause
    • Quality-of-life [ Time Frame: 1 year ]
      EORTC QLQ-BIL21
    • Overall response rate [ Time Frame: 6 week ]
      According to immune-related response criteria
    • Toxicity [ Time Frame: 6 week ]
      CTCAE V4.1


    Original Secondary Outcome:

    • Disease control rate [ Time Frame: 6 weeks ]
    • Progression-free survival [ Time Frame: 6 weeks ]
    • Duration of response [ Time Frame: 1 year ]
    • Overall survival [ Time Frame: 1 year ]
    • Quality-of-life [ Time Frame: 1 year ]
      EORTC QLQ-BIL21
    • Overall response rate [ Time Frame: 6 week ]
      According to immune-related response criteria
    • Toxicity [ Time Frame: 6 week ]
      CTCAE V4.1


    Information By: Seoul National University Hospital

    Dates:
    Date Received: February 6, 2017
    Date Started: February 25, 2017
    Date Completion: March 2019
    Last Updated: February 25, 2017
    Last Verified: February 2017