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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041068 |
E.1.2 | Term | Small cell lung cancer extensive stage |
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 overall purpose of the study is to evaluate efficacy and safety of MGN1703 administered twice weekly s.c. as switch maintenance treatment in patients with extensive disease SCLC who achieved at least PR following platinum-based first-line chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients with extensive disease SCLC ≥ 18 years of age receiving platinum-based first-line chemotherapy;
2. Extensive disease SCLC confirmed by a pathologist, on the basis of histology of SCLC or mixed histology of SCLC, or a cytological diagnosis if histology cannot be obtained;
3. Completion of 4 cycles of first-line therapy with a platinum-based regimen and no other prior chemotherapy;
4. Documented evidence of tumor response (PR or CR) as assessed by the investigator at the end of the fourth cycle of platinum-based first-line chemotherapy using CT or magnetic resonance imaging (MRI) scan;
5. Brain metastases are allowed only after cranial irradiation, if asymptomatic and not requiring continuous treatment with steroids or anticonvulsants;
6. ECOG performance status 0 or 1;
7. Adequate organ function with total bilirubin, lactate dehydrogenase [LDH], alkaline phosphatase [AP], albumin, creatinine, urea, electrolytes, and coagulation parameters ≤ 1.5 × upper limit of normal (ULN), and with aspartate aminotransferase [AST] and ALT ≤ 2.5 × ULN in the absence of liver metastases or ≤ 5.0 × ULN in the presence of liver metastases;
8. Adequate hematological parameters: absolute neutrophil count ≥ 1.0 × 109/L; platelet count ≥ 80 × 109/L; leukocyte count ≥ 2.0 × 109/L; lymphocytes ≥ 0.8 × 109/L; hemoglobin ≥ 9.0 g/dL or 5.59 mmol/L;
9. Male patients who have had vasectomy, and female patients who are not of childbearing potential (i.e. who are post-menopausal for at least 24 consecutive months or who have undergone surgical sterilization [hysterectomy, bilateral tubal ligation, or bilateral oophorectomy]). Male and female patients with reproductive potential can be included if they are using an effective means of contraception with a failure rate of less than 1% per year throughout the study, e.g. established use of oral, implanted, or injected hormonal contraceptives; placement of intra-uterine device or intra-uterine system; or use of barrier methods such as condom or diaphragm together with spermicide product;
10. Negative serum pregnancy test in women of childbearing potential;
11. Signed informed consent form (ICF).
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E.4 | Principal exclusion criteria |
1. Patients with no evidence of tumor response (PR or CR) at the end of the fourth cycle of platinum-based chemotherapy;
2. Clinically significant concomitant diseases or conditions, which, in opinion of the investigator, would lead to an unacceptable risk for the patient to participate in the study;
3. 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 patient has been disease free for more than 3 years;
4. History of carcinomatous meningitis;
5. Prior or current paraneoplastic syndrome related to SCLC;
6. Active or uncontrolled infections at the time of randomization;
7. Severe anemia requiring repeated blood cell transfusion;
8. History of autoimmune disease or immune deficiency;
9. Known hypersensitivity to oligonucleotides or excipients of the formulation;
10. Pregnant and/or nursing;
11. Chronic systemic immune therapy or immunosuppressant medication other than steroids within the last 6 weeks prior to study treatment. If the patient receives systemic steroids at the time of Screening, the dose of systemic steroids should gradually be reduced before start of treatment in the experimental arm;
12. Use of antibiotic therapy within the last 2 weeks prior to study treatment;
13. Concurrent use of molecular targeted therapy;
14. HIV seropositivity or active hepatitis B or C infection;
15. Planned major surgery during the study, except for thoracotomy;
16. Participation in another clinical study with other investigational drugs within 28 days prior to study treatment, or treatment with any anti-cancer investigational drug within 12 months prior to study treatment;
17. Vaccination within 1 month prior to study treatment;
18. Any medical, mental, psychological or psychiatric condition that in the opinion of the investigator would not permit the patient 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) |
Overall survival from the date of randomization |
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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) |
•OS from the start of the first cycle of induction chemotherapy (OS1);
• Progression-free survival (PFS) from the date of randomization with progression assessed by response evaluation in solid tumors (RECIST) 1.1 and immune-related response criteria (irRC);
• PFS from the start of the first cycle of induction chemotherapy (PFS1) assessed by RECIST 1.1 and irRC;
• Best objective response rate (ORR) with clinical response assessed by RECIST 1.1 and irRC;
• Quality of life (QoL) measured by Lung Cancer Symptom Scale (LCSS) at every staging;
• Treatment outcome correlation of predefined biomarkers and immune parameters.
The following safety assessments are considered as secondary endpoints:
• Safety profile of MGN1703 in terms of the incidence of AEs graded according to
NCI CTC Version 4.03;
• Autoimmunity of MGN1703 in terms of ANA. |
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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 | 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 | 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) | Yes |
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 | 3 |
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 | 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 study will be closed no later than 2 years from last patient in (LPI) |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |