E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced rectal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038050 |
E.1.2 | Term | Rectal cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038049 |
E.1.2 | Term | Rectal cancer stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Some patients with rectal cancer benefit from receiving chemotherapy and radiotherapy before they have an operation to remove their tumour. This trial will determine whether the addition of a second drug (irinotecan) to the standard treatment of oral chemotherapy using capecitabine and radiotherapy will result in fewer cancer recurrences (regrowth) after the operation and if patients live longer. |
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E.2.2 | Secondary objectives of the trial |
Secondary outcome measures are looking at the following: a) disease-specific survival b) local recurrence c) overall survival d) complete resection of the tumour e) complete shrinkage of the tumour after chemotherapy f) problems occuring due to surgery g) functional outcome & quality of life h) tumour cell density in specimens taken at surgery
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of primary rectal cancer - Histologically confirmed invasive adenocarcinoma - Pelvic MRI defined disease (one of the following): - Mesorectal fascia involved or breached - includes involvement of adjacent organ - Mesorectal fascia threatened (tumour ≤ 1mm from mesorectal fascia) includes:- - primary tumour ≤1mm from mesorectal fascia or - extra-mural vascular invasion ≤1mm from mesorectal fascia or - tumour deposit with irregular border and mixed signal intensity ≤1mm from mesorectal fascia - Low tumours at/below level of levators where:- - tumour ≤1mm from levator on two imaging planes or - tumour through full thickness of muscularis propria or beyond at level of puborectalis sling or below or - tumour involving the intersphincteric plane or - tumour involving the external anal sphincter - Patients with enlarged pelvic side wall nodes are eligible only if they also meet the above criteria. - Superior extent of macroscopic tumour no higher than S1/2 junction on saggital MRI - ECOG performance status 0 or 1 (see Appendix 2) - Considered fit to receive all trial treatments - Bowel function controlled with ≤6mg loperamide per day - Absolute neutrophil count >1.5x109/l; platelets >100 x 109/l - Serum transaminase <3 x ULN - Adequate renal function (Cockcroft-Gault estimation ≥50 ml/min) (see appendix 3) - Bilirubin <1.5 x ULN - Able to swallow oral medication - Willing and able to give informed consent and comply with treatment and follow up schedule - Aged 18 or over |
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E.4 | Principal exclusion criteria |
- Previous radiotherapy to the pelvis (including brachytherapy) - Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months prior to randomisation) - Unequivocal evidence of metastatic disease (includes resectable metastases) - Patients with equivocal lesions (determined at MDT) are eligible - Major disturbance of bowel function (e.g. gross faecal incontinence or requiring >6mg loperamide each day) - History of another malignancy within the last 5 years except successfully treated non-melanoma cancer of skin or carcinoma in situ of uterine cervix. - Known dihydropyrimidine dehydrogenase (DPYD) deficiency - Known Gilberts disease (hyperbilirubinaemia) - Taking warfarin that cannot be discontinued at least 7 days prior to starting treatment - Taking phenytoin or sorivudine or its chemically related anologues, such as brivudine (see section 7.9 for further details) - Gastrointestinal disorder which would interfere with oral therapy and its bioavailability - Pregnant, lactating, or pre menopausal women not using adequate contraception - Oral St John’s Wort therapy that cannot be discontinued at least 14 days prior to starting treatment - Unfit to receive any study treatment or subsequent surgical resection |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measure is disease free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed at 4 planned stages during the trial |
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E.5.2 | Secondary end point(s) |
Disease-specific survival Loco-regional failure Overall survival Histopathologically confirmed CRM-ve resection rate Histopathological complete response (pCR) rate Histopathologically quantitated tumour cell density Surgical morbidity Health-related Quality of Life (QoL) and functional outcome
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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 | No |
E.6.5 | Efficacy | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
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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For regulatory purposes the end of the trial will be 5 years after the last patient has been randomised, or once all patients have progressed or died, whichever happens first |
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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 | 10 |
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 | 10 |
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 |