E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced rectal adenocarcinoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038028 |
E.1.2 | Term | Rectal adenocarcinoma stage III |
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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 |
To assess if chemotherapy before chemoradiation can increase tumor downstaging in rectal cancer |
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E.2.2 | Secondary objectives of the trial |
Toxicity Disease free survival |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
- histologically confirmed rectal adenocarcinoma, located 0-15 cm from the anal margin, T2-4 / N+ amenable to indication for chemoradiotherapy. - patients with resectable liver or pulmonary metastases (≤3) could be included in this protocol ,providing that chemoradiation is indicated in the treatment plan. - age > 18 - WHO performance status (PS) of 0-2 at study entry - measurable (bi-dimensionally with both diameters ≥1cm) / evaluable disease - adequate renal (serum creatinin <1.5x upper reference range), liver (total bilirubin < 1.5x upper reference range) and hematopoietic function (PMN>1,5x 109/L, platelet >100x109/L), PTT ≤ 1,5 upper reference range. - life expectancy of at least 12 weeks - effective contraception throughout the study for both male and female patients if the risk of conception exist.
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E.4 | Principal exclusion criteria |
Exclusion criteria - metastatic disease not amenable to curative surgery (≥ liver, pulmonary metastases) - uncontrolled concurrent CNS, cardiac, infectious diseases - previous treatment (chemotherapy or radiotherapy) for this cancer excepted colostomy - known hypersensitivity to any components of study treatments - previous malignancy in the last past 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix - chronic inflammatory disease of the ileum or the colon - Peripheral sensory neuropathy with functional impairment - pregnancy or breast feeding - medical or psychological conditions that would not permit the patient to complete the study or sign informed consent - major surgical procedure 28 days prior to randomization - Clinically significant cardiovascular disease ( including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 12 months prior to randomisation. No other restrictions due to age or co-morbid conditions if surgery was not contraindicated.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to compare the achievement of a pT0-1 stage in each arm . The pT0-1 stage will be assessed as a binary variable. Assuming a rate of 20% pT0-1 stage in the radiochemotherapy arm, we calculated that we would need a sample of 110 patients (55 in each arm) to ensure 80% statistical power of detecting an improvement of 25% pT0-1 stage with a two-sided significance level of 0.05. Secondary end-points are tumoral and nodal down staging, sphincter preservation.
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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 | 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 | 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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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 | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |