E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The trial will include patients with so called "fusion-driven", metastatic sarcomas of the following types: - Ewing sarcoma, - alveolar rhabdomyosarcoma - or synovial sarcoma who are in first or second complete remission or partial response |
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E.1.1.1 | Medical condition in easily understood language |
The trial will include patients with soft tissue tumors with high mortality that are typically induced and driven by gene-fusion |
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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 | 10015560 |
E.1.2 | Term | Ewing's sarcoma |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065867 |
E.1.2 | Term | Alveolar rhabdomyosarcoma |
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 | 10042863 |
E.1.2 | Term | Synovial sarcoma |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess individualized fusion-petide and neopetide vaccination induced T-cell response
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E.2.2 | Secondary objectives of the trial |
• To evaluate the feasibility of individualized fusion-petide and neopetide vaccination in a population of patients at very high risk of recurrance and mortality • To assess the safety/tolerability the indivdualized IPX-Vaccine • To gather very early efficacy data by monitoring event free and overall survival as major clinically relevant endpoints for potential planning of future confirmatory / pivotal trials |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Confirmed metastatic fusion-driven sarcoma (rhabdomyo-, Ewing- and synovial sarcoma, age ≥ 2 to < 40 years) in complete remission (CR) or partial response (PR) after first therapy phase (e.g. neoadjuvant chemotherapy) • Access to whole exome sequencing and RNAseq data of the gene fusion (fusion-breakpoint RNA sequence) (by participation in INFORM, MASTER, HEROES-AYA or comparable programs). • Successful design and production of the patient-individual vaccine cocktail • Patients have reached first or second complete or stable partial remission including local therapy of the remaining residua (PRplus) at the end of cytotoxic treatment.
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E.4 | Principal exclusion criteria |
• Non-CR or progressive PR at the end of adjuvant and/or maintenance cytotoxic treatment (during screening phase) • Age < 2 or ≥ 40 years
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is "success of treatment", defined as the patient showing a vaccination-induced T cell response to either of the two patient specific peptides without unacceptable toxicity until Follow-up visit (28 ± 7 days after last vaccination). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
assessed at 28 ± 7 days after last vaccination |
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E.5.2 | Secondary end point(s) |
a. CD8+ and/or CD4+ T-cell responses measured 2-fold above background in response to either of the two patient-specific peptides (fusion-peptide and mutation-based neopeptide). b. CD8+ and/or CD4+ T-cell responses measured 2-fold above background in response to either of the two patient-specific peptides after completion of the study at day 180. c. Event-free (EFS) at day 180. d. Overall survival (OS) at day 180. e. Quality of life during study treatment.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 180 after first vaccination |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 10 |
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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |