E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with metastatic colorectal carcinoma (CRC), who have undergone a complete resection of their primary tumor and recent resection of their liver metastases (R0 or R1) with curative intent. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with metastatic colorectal cancer, who have undergone a complete resection of the colorectal cancer and recent resection of their liver metastases. |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
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 |
Comparative evaluation of recurrence-free survival time and three year overall survial between the treatment groups L-BLP25 plus cyclophosphamide versus placebo vaccination and saline infusion |
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E.2.2 | Secondary objectives of the trial |
Comparative assessment of: - Safety / Tolerability - Recurrence free survival time in the subgroup of MUC1 positive cancers - Overall survival in the subgroup of MUC1 positive cancers
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Translational protocol: MUC1 expression analysis and immuno-monitoring parameters |
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E.3 | Principal inclusion criteria |
1. Signed written informed consent. 2. Male or female. 3. At least 18 years of age. 4. Female patients of childbearing potential (and if appropriate male patients with female partners of childbearing potential) must be willing to use an adequate method of contraception for 4 weeks prior to, during and 12 weeks after the last dose of trial medication. A negative pregnancy test is required for female subjects. Adequate contraception for female subjects is defined as two barrier methods, or one barrier method with a spermicide, or intrauterine device or use of hormonal female contraceptive. 5. Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with complete resection of primary tumor and no evidence of local relapse. 6. Metastatic disease of the liver, with recent (< 6 weeks prior to randomization) resection (R0 or R1) of all liver metastases. Metastasectomy may have been either synchronous or metachronous. Any neoadjuvant therapy may have been applied for maximal 3 months prior to metastasectomy. 7. Subject has an ECOG performance status of 0 or 1. 8. Subject has adequate hematologic, hepatic, and renal function within 2 weeks prior to initiation of therapy as defined by the following: - Absolute neutrophils > 1,500/mm3 and platelets > 140,000/mm3. - Bilirubin < 1.5 x upper limit of normal (ULN). - AST and ALT < 2.5 x ULN. - Creatinine < 1.5 x ULN. - International Normalized Ratio (INR) and partial thromboplastin time (PTT) in the normal range of the local lab respectively within therapeutic range in case of anticoagulation . 9. Willingness to comply with study protocol requirements.
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E.4 | Principal exclusion criteria |
1. Metastases other than liver metastases. 2. R2 and Rx resected liver metastases. 3. Chemotherapy within 4 weeks prior to randomization 4. Receipt of immunotherapy (e.g. interferons, tumor necrosis factor, interleukins, or growth factors [GM-CSF, G-CSF, M- CSF], monoclonal antibodies) within 4 weeks (28 days) prior to randomization. 5. Any known autoimmune disease, past or current. 6. A recognized immunodeficiency disease including cellular immuno-deficiencies, hypogammaglobulinemia or dysgammaglobulinemia; hereditary or congenital immunodeficiencies. 7. Known active hepatitis B infection and/or hepatitis C infection, known human immunodeficiency virus infection, or any other infectious process that in the opinion of the investigator could compromise the subject’s ability to mount an immune response, or expose him/ her to likelihood of more and/or severe side effects. 8. Past or current history of malignant neoplasm other than CRC, except for curatively treated non-melanoma skin cancer, in-situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years. 9. Medical or psychiatric conditions that would interfere with ability to provide informed consent, communicate side effects, or comply with protocol requirements. 10. Clinically significant cardiac disease, e.g. cardiac failure of New York Heart Association classes III-IV; uncontrolled angina pectoris, uncontrolled arrhythmia, uncontrolled hypertension, myocardial infarction in the previous 12 months as confirmed by an ECG. 11. Splenectomy. 12. Previous (less than 4 weeks prior to randomization) or concurrent treatment with a non-permitted drug. 13. Pregnancy and lactation period. 14. Participation in another clinical study within 30 days prior to randomization. 15. Known hypersensitivity to the study treatment drugs. 16. Known alcohol or drug abuse. 17. Legal incapacity or limited legal capacity. Any other reason that, in the opinion of the investigator, precludes the subject from participating in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Recurrence-Free Survival (RFS) time and three year overall survival based on standard imaging. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Planned evaluation of primary endpoint: Q1 2018 |
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E.5.2 | Secondary end point(s) |
- Safety / tolerability - Recurrence free survival of MUC1 positive cancers - Overall survival time of MUC1 positive cancers MUC1 expression analyses and Immunomonitoring parameters to be defined in a separate translational protocol.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Planned evaluation of secondary endpoint: Q1 2018 |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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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End of trial is defined as three years after the last patient was randomized to the study |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |