E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced rectal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Bowel cancer |
Endetarmskræft |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010033 |
E.1.2 | Term | Colorectal cancer stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010034 |
E.1.2 | Term | Colorectal 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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10010023 |
E.1.2 | Term | Colorectal neoplasms malignant |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
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 |
The primary objectives of this study are to investigate the safety and efficacy of treating patients diagnosed with primary locally advanced rectal cancer with electrochemotherapy through an endoscopic system. |
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E.2.2 | Secondary objectives of the trial |
To investigate tumorreduction in PET/MRI, pathological tumor reduction (ypTNM), tumor regression (TRG), and intratumoral and systemic immunological response in patients diagnosed with primary locally advanced rectal cancer, treated with endoscopic assisted electrochemotherapy prior to intended curative surgery. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient must be mentally capable of understanding the information given. 2. Patients must give written informed consent. 3. Histologically verified rectal tumor. 4. Men or women aged at least 18 years. 5. Case reviewed by MDT (surgery, radiology, oncology). Case considered curable with neoadjuvant therapy followed by surgical excision (UICC stadium II-III). 6. ASA class I-III (Classification of the American Society of Anesthesiology)
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E.4 | Principal exclusion criteria |
1. Coagulation disorder. 2. Patients with ICD or pacemaker units. 3. Patients with epilepsy. 4. Pregnancy or lactation/breastfeeding. 5. Patients with known Hepatitis B/C or HIV infection. 6. Patients who have undergone treatment with bevacizumab within 4 weeks prior to enrolment in this trial. 7. Patients with concomitant use of phenytoin. 8. Patients with concomitant use of clozapine. 9. Concurrent treatment with an investigational medicinal product. 10. Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study recruitments. 11. Patients with contraindications for PET/MRI scan: • Claustrophobia. • Implanted pacemaker. • Heart-valve prosthesis. • Cochlea / stapes prosthesis. • Insulin pumps that cannot be removed. • Neuro-stimulators. • Metal clips after operations. • Other metal devices and foreign bodies. • Metal shrapnel(s). • Inserted and fixed catheters i.e. Swan-Ganz catheters. • Shunts and prosthesis. 12. Advanced tumor stage, UICC stage IV. 13. Patients with Contraindications for bleomycin: • Acute pulmonary infection. • Medical history of severe pulmonary disease. • Previous allergic reactions to bleomycin. • Previous cumulative dose of bleomycin exceeding 250mg/m2. • Pre-existing renal dysfunction. Bleomycin treatment: Creatinine clearance must be greater than 40 ml/min. • Platelet count ≤50 mia/l. • Prothrombin time ≥ 40 sec. 14. Patients registered in the Danish “Vævsanvendelsesregister”
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: Any adverse or serious adverse events
Efficacy: Reduction in tumor size prior to intended curative surgery.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety: Continuous evaluation during the trial Pain and general health questionnaire incl. LARS at follow-up (6 weeks/12 weeks)
Efficacy: Primary: Pathological evaluation of tumor (ypT/TRG) following surgery.
Secondary: PET/MRI evaluation prior to surgery. Pathological tumor reduction (ypTNM) following surgery Tumor regression (TRG) following surgery Intratumoral and systemic immunological response prior/following surgery. |
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E.5.2 | Secondary end point(s) |
Tumorreduction in PET/MRI. Intratumoral and systemic immunological response. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumorreduction in PET/MRI one week prior to surgery. Intratumoral and systemic immunological response prior/following surgery. |
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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 | 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 | 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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
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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Final follow up of last patient 12 weeks after treatment |
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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 | |