E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
All gastrointestinal and hepatobiliary cancers including colorectal cancer, cancer of unknown primary, pancreatic cancer, stomach cancer and oesophageal cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the bowel, stomach, gullet, pancreas and cancer of unknown primary site |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Does teysuno cause less cardiotoxicity than capecitabine? |
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E.2.2 | Secondary objectives of the trial |
Does the level of damage to the heart and blood vessels correlate with the level of toxic waste products from the study drug? Is the risk of developing heart damage greater in patients with pre-existing heart problems? Is the underlying mechanism that causes drug related heart damage due to an effect on the blood vessels or disruption of blood clotting?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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, cancer of unknown primary, hepatobiliary or pancreatic cancer. • 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 creatinine clearance (Cockcroft and Gault, adjusted for BSA>50 mL/min or estimated glomerular filtration rate (eGFR) or measured GFR (EDTA clearance) >30 mL/min. [Patients with Cr Cl 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.
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E.4 | Principal exclusion criteria |
• Patients who are unfit for the chemotherapy regimens in this protocol, such as: - Severe uncontrolled concurrent medical illness (including poorly controlled angina or very recent MI, i.e. in previous 3 months) likely to interfere with protocol treatments - 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 DELETED • Patients on therapeutic anticoagulation (warfarin or LMWH). • Patients unable to lie flat. DELETED • Patients unable to withstand the visits and cardiovascular investigations proposed within the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
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 3 days between day 5 and day 7. Data will be analysed on a Pathfinder Digital Analyser. All analyses will be carried out by a blinded observer. The electrocardiogram will be visually inspected for quality and if satisfactory will be analysed using the automated algorithms within the software package. The baseline ST segment deviation will be determined as the average of the entire 24-hour period, and will be set for each lead (II, V2 and V5 –representative of the inferior, anterior and lateral walls of the heart respectively) separately. After the baseline is set, the automated algorithm will determine episodes of ST deviation that meet the criteria and will subsequently be recorded. Number and duration of ST changes will be reported. Ischemic episodes are defined as > 1 mm (0.1 mV) ST deviation, measured at the J-point + 80ms and lasting > 60 seconds. The co-investigators have experience with this technique, which has been used to detect cardiac ischaemia induced by diesel pollution. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The study participants will be monitored continuously by ECG for 3 days (preferably days 5-7, but may be performed at any point between days 3-10). |
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E.5.2 | Secondary end point(s) |
Does the level of damage to the heart and blood vessels correlate with the level of toxic waste products from the study drug? Is the risk of developing heart damage greater in patients with pre-existing heart problems? The underlying mechanism that causes drug related heart damage due to damage of the blood vessels or disruption of blood clotting?
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be measured at baseline and after 7, 14 and 21 days of taking the study drug |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |