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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To optimise the dose of oral 5-ALA administration for intra-operative fluorescence diagnosis of metastatic lymph nodes in colon cancer.
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E.2.2 | Secondary objectives of the trial |
1) Establish a reliable and repeatable methodology for fluorescence diagnosis of lymph node metastasis by standardisation of: i) pre-operative CT lymph node reporting ii) intra-operative fluorescence detection system iii) surgical technique for laparoscopic segmental colonic resection with D3 lymphadenectomy iv) histopathogical examination of resected specimens. 2) identify systemic, operative and patient factors which adversely affect the intraoperative detection of lymph node fluorescence.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Able to give informed consent and willing to follow trial protocol • Aged over 18 • Patients with cancers of the right and sigmoid colon amenable to laparoscopic resection incorporating D3 lymphadenectomy, as agreed by MDT discussion following histopathological diagnosis and radiological staging. Where possible, the study population will be enriched with locally advanced colon cancers to obtain as much information as possible on 5-ALA FD for lymph node metastases. • Patients with distant metastatic disease will be eligible, provided laparoscopic resection of the cancer is part of routine clinical care. • Fit for standard laparoscopic resection • American Society of Anesthesiologists (ASA) classification ≤ 3 • Normal hepatic and renal function i) Total bilirubin within normal institutional limits, AST/ALT < 2.5 X institutional upper limit of normal ii) Creatinine within normal institutional limits
Evaluation phase: a separate protocol and application will be submitted
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E.4 | Principal exclusion criteria |
• Patients with cancers of the transverse and left colon (due to difficulty in defining D3 lymphadenectomy in these anatomical locations) • Past history of hypersensitivity reactions to 5-ALA or colorimetric dye. • Acute or chronic porphyria or a family history • Patients with synchronous colonic or rectal cancer (but not benign polyps) • Patients with co-existent inflammatory bowel disease, such as Crohn’s disease, ulcerative colitis or active diverticulitis, which may influence the lymphatic uptake of 5-ALA • Pregnant (positive pregnancy test) or breast feeding. 5-ALA has unknown teratogenic and abortifacient effects. • Received an investigational medicinal product at any dose within 28 days before registration • Poorly controlled or serious medical or psychiatric illness that, in the Investigator’s opinion, is likely to interfere with participation and/or compliance in this clinical trial.
Evaluation phase: a separate protocol and application will be submitted |
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E.5 End points |
E.5.1 | Primary end point(s) |
We aim to undertake a two-staged investigation
Developmental Phase: Identification of the optimal dose for oral administration of 5-ALA for the accurate intra-operative detection of lymph node metastases. Evaluation Phase: a separate protocol and application will be submitted for this phase. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Both centres will recruit at least 20 patients over a period of 18 months |
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E.5.2 | Secondary end point(s) |
1) Establish a reliable and repeatable methodology for fluorescence diagnosis of lymph node metastasis by standardisation of: i) pre-operative CT lymph node reporting ii) intra-operative fluorescence detection system iii) surgical technique for laparoscopic segmental colonic resection with D3 lymphadenectomy iv) histopathogical examination of resected specimens. 2) identify systemic, operative and patient factors which adversely affect the intraoperative detection of lymph node fluorescence.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Both centres will recruit at least 20 patients over a period of 18 months |
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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 | Yes |
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) | 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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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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The end of the trial is defined as the date all histopathology results from resected samples have been evaluated or the end of the period of serious adverse event notification, that is 30 days after the last participant has received 5 ALA. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |