E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced colorectal carcinoma (AJCC Stage IV) with disease control after initial first-line therapy |
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E.1.1.1 | Medical condition in easily understood language |
Patients with advanced metastatic colorectal carcinoma which responded to disease control after an initial first line chemotherapy |
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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 | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010036 |
E.1.2 | Term | Colorectal carcinoma |
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 objective of this study is to demonstrate that the efficacy variables of MGN1703 in the maintenance treatment of patients with advanced colorectal carcinoma with disease control after initial first-line therapy is superior to placebo. For this purpose median PFS in both treatment groups will be evaluated.
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E.2.2 | Secondary objectives of the trial |
Assessment of PFS rate in both groups at landmarks 12, 18 and 24 weeks after treatment start, afterwards every 12 weeks until treatment stop Evaluation of median OS Assessment of OS proportion in both groups at the same landmarks Evaluation of ORR Evaluation of duration of response as time from initial determination of response to progressive disease measured by RECIST Assessment of the dynamic of clinical and laboratory parameters in terms of physical examination, ECOG, and CEA Evaluation of immunologic response to MGN1703 in terms of assessment of cytokine/chemokine, frequency and activation status of cell subpopulations, and cell culture in-vitro test and analysis of blood mRNA Assessment of quality of life Assessment of the safety profile of MGN1703 in terms of incidence and severity of adverse events graded according to NCI CTCAE Assessment of autoimmunity of subcutaneously administered MGN1703 in terms of rheumatoid factor, antinuclear antibodies, and anti-ds DNA antibodies |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects fulfilling the following criteria are eligible for participation in the study:
1. Male and female subjects older than 18 years of age 2. Histologically confirmed colorectal carcinoma 3. Radiological confirmation of unresectable advanced colorectal carcinoma (AJCC Stage IV) prior to start of initial first-line therapy 4. At least one measurable lesion according to RECIST measured within 2 weeks prior to treatment start in case of partial response or stable disease 5. Prior initial first-line therapy included oral or intravenous fluoropyrimidines/leucovorin, irinotecan or oxaliplatin with or without a standard dose of bevacizumab lasted between 4.5 and 6 months and finished (last day of last cycle) within 2 weeks prior to treatment start (treatment duration with irinotecan or oxaliplatin should not be less than 3 months) 6. Patients who achieved disease control measured as objective response or disease stabilization after initial first-line therapy 7. No curative standard therapy is available for the patient after first-line treatment 8. Adequate organ function, hemoglobin > 9 g/L, white blood cell count (WBC) > 3.0 x 109/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x109/L, aspartate and alanine aminotransferase (AST and ALT) < 2.5 x ULN, bilirubin < 1.5 x ULN, blood creatinine < 1.5 X ULN, prothrombin time (PT) and activated thromboplastin time (aPTT) within normal range 9. Negative pregnancy test in women with childbearing potential 10. Expected adequacy of follow-up 11. Signed informed consent form (ICF).
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will be excluded from the study: 1. More than one line of systemic chemotherapy for metastatic colorectal carcinoma 2. Tumor progression after initial first-line therapy 3. Clinically significant concomitant diseases or conditions unrelated to the underlying malignancy or chemotherapy, which in opinion of the investigator would lead to an unacceptable risk for the subject to participate in the study 4. Prior or current other malignancy, except adequately treated superficial bladder cancer, basal or squamous cell carcinoma of the skin or other cancer for which the subject has been disease free for more than 3 years 5. Known central nervous system metastases 6. Active or uncontrolled infections 7. Transfusion-dependent anemia 8. History of autoimmune disease or immune deficiency 9. Known hypersensitivity to oligonucleotides or excipients of the formulation 10. Pregnancy and/or nursing 11. Concurrent chronic systemic immune therapy or immunosuppressant medication, including steroid treatment 12. Concurrent chemotherapy, hormonal therapy (except hormonal contraception and hormonal replacement therapy for menopausal women), or immunotherapy within the last 2 weeks prior to randomization or during the conduct of the study 13. Concurrent radiotherapy within the last 6 months prior to randomization or during the conduct of the study 14. HIV seropositivity or active hepatitis B or C infection 15. Planned major surgery during the study 16. Participation in another clinical study with other investigational drugs within 14 days prior to the first treatment day 17. Vaccination within 3 months prior to the first treatment day 18. Any medical, mental, psychological or psychiatric condition which in opinion of the investigator would not permit the subject to complete the study or understand the patient information 19. Presence of drug and/or alcohol abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this clinical study is the median PFS in both treatment groups and their comparison by means of a log rank test. The level of significance will be stipulated to α = 5 %. Moreover, the PFS rates will be analyzed by means of Mantel-Haenszel tests stratified by centre. The survival curves will be presented by means of Kaplan-Meier curves. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The evaluation of the efficacy and safety endpoints will be conducted after the treatment with the investigational drugs is finished in all study participants, or when all 74 (65 x 1.125 due to 2:1 randomization) statistically calculated events occurred. |
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E.5.2 | Secondary end point(s) |
Progression-free survival (PFS) rate at landmark of 12, 18 and 24 weeks after treatment start, and afterwards every 12 weeks until treatment stop, median overall survival (OS), overall survival rate at the same landmark, objective response rate (ORR), and duration of response as time from initial determination of response to progressive disease, measured by RECIST, dynamic of clinical and laboratory signs, dynamic of immunologic response, and quality of life. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The evaluation of the efficacy and safety endpoints will be conducted after the treatment with the investigational drugs is finished in all study participants, or when all 74 (65 x 1.125 due to 2:1 randomization) statistically calculated events occurred. |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Czech Republic |
France |
Germany |
Russian Federation |
United Kingdom |
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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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Last visit of the last subject |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |