Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
Same as current

Summary

Conditions
Gallbladder Cancer
Type
Interventional
Phase
Phase 2
Design
Allocation: Non-RandomizedIntervention Model: Parallel AssignmentMasking: None (Open Label)Primary Purpose: Supportive Care

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

The ABC02 treatment regime was established in 2010 following publication in the New England Journal of Medicine and has since become the standard of care treatment of bile duct cancers otherwise known as cholangiocarcinomas, as well as gallbladder cancer. The treatment consists of gemcitabine and ci...

The ABC02 treatment regime was established in 2010 following publication in the New England Journal of Medicine and has since become the standard of care treatment of bile duct cancers otherwise known as cholangiocarcinomas, as well as gallbladder cancer. The treatment consists of gemcitabine and cisplatin given synergistically. This combination has been shown to yield an overall survival advantage of 3.6 months compared to when gemcitabine is given on its own, with additional improvements in performance status and tumour control in patients. Currently, the ABC02 regime includes a long hydration schedule based on previous use of high doses of cisplatin and perhaps historically the lack of efficacious antiemetics. Cisplatin is often associated with severe nausea and vomiting that lead to dehydration. In fact, cisplatin is a direct nephrotoxin, owing to its pro-inflammatory action in the kidneys and being able to cause immediate vasoconstriction of renal microvasculature on administration, and this coupled with its effect to induce dehydration due to nausea and vomiting, prevented the inclusion of cisplatin into many combinational regimens. 50% of patients in initial studies were found to suffer from nephrotoxicity on cisplatin and thus the administration of intravenous saline to combat this effect by inducing diuresis has also been standard of care when giving cisplatin chemotherapy. However, it is still not known what the optimal hydration solution and procedure are as there are no studies comparing either of these factors. Akynzeo is a mixture of both a 5HT3 blocker palonosetron and a neurokinin 1 inhibitor netupitant. Together the drugs are able to combat nausea and vomiting during the acute phase and delayed phase after chemotherapy. The introduction of 5HT3 blockers cut the incidence of acute nausea and vomiting in chemotherapy patients considerably, but in fear of the historical nephrotoxicity, copious volumes of IV saline remains part of the regime. This entire procedure takes 8 hours for delivery and risks fluid overload often requiring diuretic management. For reference: gemcitabine is an antimetabolite and works by imitating a pyrimidine and replacing the cytidine in nucleic acid during DNA replication. By doing so, gemcitabine halts tumour growth as actual nucleosides cannot be attached to this faulty nucleoside and this results in apoptosis. Cisplatin on the other hand is an alkylating agent and kills cancer cells by binding to DNA and interfering with its repair mechanism; upon binding to DNA it further attracts other DNA repair proteins to irreversibly bind to the structure distorting its shape and inducing apoptosis.

Tracking Information

NCT #
NCT04362449
Collaborators
Chugai Pharma UK Limited
Investigators
Principal Investigator: Harpreet Wasan, MD Gastrointestinal Clinical Research Lead and Consultant Oncologist