E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic colorectal cancer |
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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 | 14.0 |
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 |
To investigate the efficacy of IMM-101 in combination with radiation induced tumour necrosis (induced by CyberKnife treatment) in patients with colorectal cancer with metastatic disease who have received prior chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of IMM-101 in combination with radiation induced tumour necrosis (induced by CyberKnife treatment) in patients with colorectal cancer with metastatic disease who have received prior chemotherapy
To conduct an eploratory investigation of selected markers of tumour burden and immunological status in patients with colorectal cancer with metastatic disease treated with IMM-101 and radiation induced tumour necrosis (induced by CyberKnife treatment).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Are male or female; aged ≥18 years.
2. Have a histologically confirmed colorectal adenocarcinoma.
3. Have documented evidence of disease progression following at least one line of chemotherapy.
4. Have no further standard chemotherapy options available or the patient has refused further chemotherapy.
5. Have metastatic lesions in at least two sites in the liver (+/- other sites) suitable for bidimensional and volumetric evaluation by CT scan.
6. Have WHO performance status of 0-2.
7. Have a Cockcroft calculated Glomerular Filtration Rate of > 40mL/min at screening.
8. Have a life expectancy, in the opinion of the Investigator, of >3 months from screening.
9. Provide written informed consent to participate as shown by a signature and date on the patient's informed consent form (ICF).
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E.4 | Principal exclusion criteria |
1. Patient has evidence of central nervous system metastasis.
2. Patient has severe, active uncontrolled infection requiring systemic antibiotics, antiviral or antifungal treatments.
3. Patient has any previous or concurrent malignancy, except adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin and/or non-melanoma skin cancer, or if previous malignancy was more than 5 years earlier and there are no signs of recurrence.
4. Patient has serum albumin < 30 g/L at screening.
5. Patient has a C-reactive protein (CRP) > 70 mg/L at screening.
6. Patient has transaminases (ALT or AST) > 5 X Upper Limit of Normal at screening.
7.Patient has a bilirubin level > 2 X Upper Limit of Normal at screening.
8. Patient has had radiotherapy in the 12 weeks before screening.
9. Patient has used depot corticosteroids in the 6 weeks before screening.
10. Patient has had chronic use of any systemic corticosteroids (>10 mg per day of prednisolone or equivalent for a period of 2 weeks or more) and/or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporin) within the 2-week period before the first administration of study drug.
11. Patient of child-bearing potential who is not using an approved method of birth control (e.g., physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device [IUD]). Those patients that utilise hormonal contraceptives must have used the same method for at least three months before study dosing.
Patients of non-child-bearing potential are defined as having 12 month amenorrhoea or are surgically sterile.
12. Patient who is pregnant, breast feeding or planning a pregnancy during the course of the study. Where appropriate, a pre-treatment serum pregnancy test measuring human chorionic gonadotrophin (hCG) must be negative.
13. Patient has been administered any investigational product in the 3 months before screening.
14. Contraindication to CT scan, e.g., allergy to iodine based contrast medium.
15. Patient has a surgical or medical condition which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
16. Patient has presence of any uncontrolled concomitant disease (e.g., unstable angina pectoris, congestive heart failure, myocardial infarction, cardiac arrhythmias, uncontrolled severe hypertension) which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
17. Patient has a history of serious adverse reaction or serious hypersensitivity to any drug that in the opinion of the Investigator may raise a safety concern.
18. Patient has had any previous treatment with IMM-101 or related mycobacterial immunotherapy (prior BCG vaccination against TB is allowed).
19. Patient is known to have a history of human immunodeficiency virus (HIV) or syphilis, current symptomatic Hepatitis B or C.
20. Patient is unable or unwilling to comply with the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
The disease stabilisation rate at 24 weeks defined as the proportion of patients with a complete response, partial response or stable disease in accordance with immune-related response criteria. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Objective response rate at 12, 24, 36 and 48 weeks
Disease stabilisation rate at 12, 36 and 48 weeks
Overall disease stabilisation rate
Overall response rate
Progression-free survival at 12, 24, 36 and 48 weeks
Survival at 12, 24, 36 and 48 weeks
Tumour Markers at 12, 24, 36 and 48 weeks
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
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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End of study is defined as last visit of last patient |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |