A Phase 2 interventional study of Teysuno and Capecitabine in Gastrointestinal Cancer, Cancer of Unknown Primary Site and Pancreatic Cancer, sponsored by University of Edinburgh. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2023-05-12.
Sponsored by University of Edinburgh · Phase 2, Interventional, and Treatment
Capecitabine is a chemotherapy drug used to treat many types of cancer including bowel and stomach cancer. Unfortunately a side effect of this drug is that it causes heart problems including heart attacks. An alternative drug, called teysuno is used extensively in other countries instead of capecitabine and appears to have less of a bad effect on the heart whilst still killing cancer cells. This study will investigate the effect of these two drugs on the heart and blood vessels and will be the first of its kind in humans.
Fluoropyrimidines (FPs) are widely used chemotherapy agents for the management of patients with colorectal, breast, upper gastrointestinal, head and neck cancers. Capecitabine is an oral prodrug of 5-fluorouracil (5FU) which is used extensively in the UK but is associated with clinically overt cardiotoxicity in up to 9% of patients. Cardiotoxicity occurs more commonly in patients with cardiovascular disease and manifests as chest pain, myocardial infarction, congestive heart failure, or sudden death with a mortality as high as 30%. In a study of continuous ECG Holter monitoring in patients receiving 5FU infusion, the majority (68%) of patients had ischaemic ECG changes and 2 patients died suddenly. We conducted a national survey of UK oncologists and 60% felt that 5FU/capecitabine cardiotoxicity was a significant problem in their clinical practice.
Hypotheses for this toxicity include ischaemia secondary to coronary artery spasm, direct endothelial cell toxicity, myocardial toxicity and interactions with the coagulation system. Studies implicate a catabolite of 5FU, in particular fluoro-alanine (FBAL). FBAL is further metabolized to fluoroacetate (FAC), a cardiac toxin that inhibits mitochondrial aconitase, resulting in cell death.
Teysuno is an oral fluoropyrimidine that has recently obtained a European licence. It is a combination of tegafur (5-FU prodrug), gimeracil (dihydropyrimidine dehydrogenase (DPD) inhibitor) and oteracil (phosphorylation inhibitor). There have been no reports of cardiac toxicity with teysuno. The incorporation of a DPD inhibitor should reduce FBAL concentrations which may prevent FP cardiotoxicity. However, this remains to be established.
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Baseline laboratory tests (within 1 week prior to starting treatment):
Exclusion Criteria:
Patients who are unfit for the chemotherapy regimens in this protocol, such as:
Capecitabine 1250 mg/m2 twice daily, days 1-14 every 21 days
Drug: Capecitabine
Capecitabine 1000 mg/m2 twice daily, days 1-14 every 21 days (in frail or elderly patients, a CAP dose of 750 mg/m2 BD should be considered). Oxaliplatin will be given as an iv infusion at a dose of 130 mg/m2 over 2-6 hours on day 1.
Drug: Capecitabine
Teysuno will be administered at a dose of 30 mg/m2 twice daily, for 14 days, with a subsequent 7-day rest period. Patients will be assigned a dose on the basis of body surface area (BSA) and will receive one of the following doses twice daily: 40mg (BSA \< 1.5 m2), 45 mg (BSA 1. 5 to \< 1.7 m2), 55mg (BSA 1.7 - 1.9 m2),
Drug: Teysuno
Teysuno will be administered orally at a dose of 25mg/m2 twice daily, days 1-14 every 21 days Patients will be assigned a dose on the basis of body surface area (BSA) and will receive one of the following doses twice daily: 35mg (BSA \< 1.5 m2), 40mg (BSA 1.5 to \< 1.7 m2), 45mg (BSA 1.7 - 1.9 m2), 50mg (BSA \>1.9 m2). Oxaliplatin will be given as an iv infusion at a dose of 130 mg/m2 over 2-6 hours on day 1.
Drug: Teysuno
Also known as: Tegafur / Gimeracil / Oteracil
Also known as: Xeloda tablets
The primary endpoint of the study will be a difference in the duration of ST deviation pre-treatment and during treatment.
This will be recorded using Del Mar Reynolds Lifecard CF/Lifecard 12 recorders, which will record 12 leads over 24 hours and continuously if the storage card is changed daily. Pre-treatment control ECGs will be recorded for 24 hours. Continuous 12-lead monitoring shall be recorded for three days between day 5 and 7 of treatment.
Time frame: Pre treatment and between day 5-7
Plan to share: Yes — Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) will be shared with other researchers on request
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: 1 year after completion of study until 5 years after archiving
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This study is completed, as verified in May 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Tegafur-gimeracil-oteracil · Capecitabine