None listed
Conditions
Brief summary
Proton pump inhibitors (PPIs) are very common medications used for managing gastritis and reflux. Patients on chemotherapy tend to have more problems with gastritis and reflux and approximately 20-55% patients on chemotherapy are reported to be on PPIs. Capecitabine is a tablet form of chemotherapy widely used to treat cancer and has to be absorbed in the gut to be effective. Recent studies have raised concerns that individuals on capecitabine who are also prescribed with PPIs may have poorer cancer survival outcomes compared to those who are not on PPIs. One suggestion is that changes in the pH of the stomach from PPI use, affects the dissolution of the tablet and decreases how much capecitabine enters the body.In late 2019, the NZ regulatory body MEDSAFE advised NZ oncologists that there may be a possible interaction between PPI drugs and capecitabine, but fell short of making any specific recommendations due to the paucity of good quality data. To address this very real and relevant concern, we plan to conduct a study that will help us determine whether pantoprazole, an approved PPI, affects capecitabine absorption. The study will be conducted in Auckland City Hospital and will involve 20 patients who are scheduled to receive capecitabine for their bowel or breast cancer treatment. The study will span the first 2 cycles (6 weeks) of their capecitabine treatment. Each participant will receive a short course of pantoprazole either before their first or second cycle of capecitabine (cross over design). Whether they receive pantoprazole before the first or second cycle will be randomly assigned (randomization). On the first day of both cycles of capecitabine, blood and urine samples will be collected over an 8 hour period. The samples will be analysed to determine how much capecitabine was absorbed and processed in each participant (pharmacokinetic study). This will allow us to compare if the short course of pantoprazole had any effects on capecitabine.
Interventions
Consented participants who are scheduled for capecitabine monotherapy for breast or gastrointestinal cancer will be randomly allocated to receive concomitant oral pantoprazole 40mg daily, 4 days prior to and on the first day (total 5 doses) of either the first (group A) or second (Group B) cycle of capecitabine. Pharmacokinetic blood and urine sampling for capecitabine will be performed over eight hours on both cycle1 day 1 and cycle 2 day 1 to determine if PK parameters are different with panto
Consented participants who are scheduled for capecitabine monotherapy for breast or gastrointestinal cancer will be randomly allocated to receive concomitant oral pantoprazole 40mg daily, 4 days prior to and on the first day (total 5 doses) of either the first (group A) or second (Group B) cycle of capecitabine. Pharmacokinetic blood and urine sampling for capecitabine will be performed over eight hours on both cycle1 day 1 and cycle 2 day 1 to determine if PK parameters are different with pantoprazole. Participants will be contacted by phone a day before their course of pantoprazole begins and will receive a daily text reminder on the subsequent 4 days. A medication diary will be kept. The washout period is 21 days (in between cycle 1 day 1 and cycle 2 day 1)
Sponsors
Auckland District Health Board
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
adults (18+ years) with histologically confirmed GI or breast cancer, receiving adjuvant or palliative capecitabine monotherapy within the Regional Cancer and Blood Services, Auckland District Health Board. Adequate functional status (ECOG 2 or less) and organ function as defined as (i) Neutrophil>1.5, Hb>9g, Platelet>100,000, (ii) Bilirubin<1.5x ULN, ALT, AST <2.0 ULN, (iii) Creatinine clearance calculated by Cockcroft Gault >50ml/min within 14 days of cycle 1.
Exclusion criteria
Previous capecitabine use, recent Proton pump inhibitors (PPI), /H2 Receptor Blocker or antacid use, pre-existing gastritis/ gastro-oesophageal reflux necessitating treatment, previous intolerance to PPI and any condition deemed by study investigators to significantly affect normal gastrointestinal tract function (e.g. upper gastrointestinal tract surgery/ radiation/ pre-existing condition)
Outcome results
None listed