Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)

Sponsor
AHS Cancer Control Alberta
Study ID
NCT05451043
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — BIOLOGICAL
    It is a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 with the PD-1. Durvalumab is known as a checkpoint inhibitor drug
  • Gemcitabine — DRUG
    Gemcitabine is a nucleoside analog and a chemotherapeutic agent. As a prodrug, gemcitabine is transformed into its active metabolites that work by replacing the building blocks of nucleic acids during DNA elongation, arresting tumour growth and promoting apoptosis of malignant cells
  • Nab paclitaxel — DRUG
    Nanoparticle albumin-bound (nab) paclitaxel is a form of paclitaxel which works as an antimicrotubule agent. Paclitaxel, the active ingredient in nab-paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This interferes with the normal dynamic reorganization of the microtubule network required for interphase and mitotic functions
  • Tremelimumab — BIOLOGICAL
    Tremelimumab is a fully human monoclonal antibody against CTLA-4. It is an immune checkpoint blocker.
  • Propranolol — DRUG
    Competitively blocks both β1 and β2 adrenergic receptors.
  • Cisplatin — DRUG
    cisplatin has been associated with ability to crosslink with the urine bases on the DNA to form DNA adducts, preventing repair of the DNA leading to DNA damage and subsequently induces apoptosis within cancer cells.

Study Details

A single-arm, interventional study combining Immunotherapy and propranolol with/without chemotherapy and propranolol 1. Pancreatic Cancer Durvalumab will be administered once every 4 weeks, in combination with gemcitabine + nab-paclitaxel (day 1/8/15) and continuous propranolol. Tremelimumab will be given on day 1 of cycle 1, which may be repeated at the time of progression in eligible patients. 2. HCC Durvalumab will be administered once every 4 weeks in combination with continuous propranolol. Tremelimumab will be given on day 1 of cycle 1, which may be repeated at the time of progression in eligible patients. 3. Biliary Tract Cancer (BTC, Cholangiocarcinoma of the gallbladder or bile ducts) Durvalumab will be administered once every 3 weeks, in combination with cisplatin + gemcitabine (day 1/8) and continuous propranolol. Tremelimumab will be given on day 1 of cycle 1, which may be repeated at the time of progression in eligible patients.

Key Dates

Start date
Jul 5, 2023
Status verified
Jun 2025
Primary completion
Oct 1, 2026
Completion
Oct 1, 2029

Study Design

Enrollment
62 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Pancreatic Cancer
    Durvalumab will be administered once every 4 weeks, in combination with gemcitabine + nab-paclitaxel (day 1/8/15) and continuous propranolol. Tremelimumab will be given on day 1 of cycle 1, which may be repeated at the time of progression in eligible patients.
  • Experimental: Hepatocellular Cancer
    Durvalumab will be administered once every 4 weeks in combination with continuous propranolol. Tremelimumab will be given on day 1 of cycle 1, which may be repeated at the time of progression in eligible patients.
  • Experimental: Biliary Tract Cancer
    Durvalumab will be administered once every 3 weeks, in combination with cisplatin + gemcitabine (day 1/8) and continuous propranolol. Tremelimumab will be given on day 1 of cycle 1, which may be repeated at the time of progression in eligible patients.

Primary Outcome Measure

Investigating and establishing the efficacy of propranolol in boosting the effects of immunotherapy in pancreatic adenocarcinoma [ Time Frame: Assessed one year after enrollment of last participant ]

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