Study to Compare Cardiovascular Side Effects of Teysuno Versus Capecitabine

NCT01845337 | Completed Phase 2 DMC

• 1 other identifier: 2012-005282-12
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastrointestinal Cancer; Cancer of Unknown Primary Site; Pancreatic Cancer; Bile Duct Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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.

  Pre treatment and between day 5-7

Study Arms (4)

Capecitabine single agent

ACTIVE COMPARATOR

Capecitabine 1250 mg/m2 twice daily, days 1-14 every 21 days

Drug: Capecitabine

Capecitabine /Oxaliplatin

ACTIVE COMPARATOR

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 single agent

ACTIVE COMPARATOR

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/ Oxaliplatin

ACTIVE COMPARATOR

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

Interventions

Teysuno DRUG

Also known as: Tegafur / Gimeracil / Oteracil

Teysuno single agent; Teysuno/ Oxaliplatin

Capecitabine DRUG

Also known as: Xeloda tablets

Capecitabine /Oxaliplatin; Capecitabine single agent

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients at least 18 years or over with no upper age limit.
• Confirmed advanced or metastatic oesophageal, gastric, gastro-oesophageal, small bowel, colorectal, hepatobiliary or pancreatic cancer or cancer of unknown primary.
• Suitable for treatment with fluoropyrimidine, either alone or in combination with oxaliplatin.
• WHO performance status (PS) 0, 1 or 2 and considered by responsible consultant to be fit to undergo planned chemotherapy and cardiac investigations.
• Baseline laboratory tests (within 1 week prior to starting treatment):
• Neutrophils \>1.5 x109 /L and platelet count \> 100 x109 /L
• Serum bilirubin \<1.5 x upper limit of normal (ULN), alkaline phosphatase \<5x ULN, and serum transaminase (either AST or ALT) \<3 x ULN
• Estimated glomerular filtration rate (eGFR) \>30 mL/min (Patients with eGFR 30-50 mL/min will be included but should be treated at a reduced dose (see master prescription chart).
• For women of childbearing potential; negative pregnancy test and adequate contraceptive precautions.
• Effective contraception for male patients if the risk of conception exists.
• Written informed consent for participation in the trial.

You may not qualify if:

• Patients who are unfit for the chemotherapy regimens in this protocol, such as:
• Known intolerance to CAP or other FPs
• Severe uncontrolled concurrent medical illness likely to interfere with protocol treatments
• Poorly controlled angina or MI in previous 6 months
• Any psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication
• Partial or complete bowel obstruction
• Pre-existing neuropathy \> grade 1 if combination therapy proposed
• Patients on therapeutic anticoagulation (warfarin or LMWH).
• Patients unable to lie flat.
• Patients unable to withstand the visits and cardiovascular investigations proposed within the study.

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Edinburgh Cancer Centre

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Neoplasms, Unknown Primary; Pancreatic Neoplasms; Bile Duct Neoplasms

Interventions

tegafur-gimeracil-oteracil; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Sally Clive, MBChB

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 3, 2013
• Study Start: February 5, 2014
• Primary Completion: March 18, 2020
• Study Completion: October 8, 2020
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 1 year after completion of study until 5 years after archiving

Locations

GB (1)