E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10047065 |
E.1.2 | Term | Vascular disorders |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10040785 |
E.1.2 | Term | Skin and subcutaneous tissue disorders |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10018065 |
E.1.2 | Term | General disorders and administration site conditions |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10017947 |
E.1.2 | Term | Gastrointestinal disorders |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
Lymph node staging:
- To determine the diagnostic performance of gadofosveset-enhanced T1-weighted MR imaging for the discrimination between pN0 and pN+ patients for both primary staging and restaging after chemoradiotherapy
Tumour response evaluation after CRT:
- To determine the diagnostic value of DWI for the assessment of response after chemoradiotherapy, compared to standard T2-weighted MR imaging only
- To determine the diagnostic value of DCE-MRI for the assessment of response after chemoradiotherapy, compared to standard T2-weighted MR imaging only
Early response prediction during CRT:
- To determine the predictive value of the change in ADC two weeks after start of CRT compared to ADC before CRT for identifying good responders.
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E.2.2 | Secondary objectives of the trial |
1. To determine the inter-observer agreement for the imaging techniques under investigation (gadofosveset-enhanced MRI for nodal assessment, DWI and DCE-MRI for the tumour response assessment after chemoradiotherapy) and the differences between expert vs. non-expert readers and general vs. referral centres
2. To compare the over- and understaging rates for all the techniques under investigation with the conventional imaging.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Biopsy proven primary rectal cancer (≤15 cm from the anorectal verge as measured on MRI)
- Age >18 years
- Written informed consent
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E.4 | Principal exclusion criteria |
- Ineligibility to undergo MRI (claustrophobia, pacemaker, non-MR compatible surgical implants, metal fragments in the eye)
- Pregnancy
- Locally recurrent rectal cancer
- A history of severe allergy to contrast agents
- Ineligibility to receive gadofosveset contrast (history of contrast allergy, impaired kidney function with a Glomerular Filtration Rate <30 ml/min/1.73m2
- Incurable disease due to metastases or co-morbidity
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is the diagnostic performance of the techniques under investigation (gadofosveset-enhanced MRI for nodal assessment and DWI for the tumour response assessment after chemoradiotherapy). Histopathology will be used as gold standard of reference. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At completion of inclusion and follow-up |
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E.5.2 | Secondary end point(s) |
1. To determine the inter-observer agreement for the imaging techniques under investigation (gadofosveset-enhanced MRI for nodal assessment, DWI and DCE-MRI for the tumour response assessment after chemoradiotherapy) and the differences between expert vs. non-expert readers and general vs. referral centres
2. To compare the over- and understaging rates for all the techniques under investigation with the conventional imaging. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At completion of inclusion and follow-up |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
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 | No |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |