The PerVision trial utilizes an approach of a patient-individual cancer vaccine with sarcoma-specific peptides in metastasized fusion-driven sarcoma patients determined by next generation whole exome sequencing of tumor and normal tissue as well as RNA sequencing of the tumor. This approach is applicable to all patients independent of the expression of distinct tumor associated antigens, and independent of their human leukocyte antigen-typing (HLA-typing). The results of this study can directly be translated to other tumor entities. It is an interventional, multicenter, open-label, phase I/II feasibility and early proof of concept study evaluating a personalized peptide vaccine. Primary objective is to evaluate safety and success of treatment, the latter be defined as vaccination-induced T-cell response without unacceptable toxicity.
The PerVision trial utilizes an approach of a patient-individual cancer vaccine with sarcoma-specific peptides (one peptide derived from the sarcoma-specific fusion breakpoint, 'fusion-peptide', and a second peptide derived from neoantigens derived from patient-specific non-synonymous mutations with the highest prediction score, 'mutation-based neopeptide') in metastasized fusion-driven sarcoma patients determined by next generation whole exome sequencing of tumor and normal tissue as well as RNA sequencing of the tumor. This approach is applicable to all patients independent of the expression of distinct tumor associated antigens, and independent of their human leukocyte antigen-typing (HLA-typing). The results of this study can directly be translated to other tumor entities. It is an interventional, multicenter, open-label, phase I/II feasibility and early proof of concept study evaluating a personalized peptide vaccine and the toll like receptor (TLR) 1/2 ligand XS15 emulsified in Montanide ISA 51 VG in fusion driven sarcoma patients. The principal questions are: 1. To investigate, whether it is possible to induce a mutation-specific immune response in sarcoma patients and young adults after salvage chemotherapy 2. To investigate possible side effects and toxicity of the treatment 3. To gather indications if our approach has a beneficial effect on residual disease as well as event free survival (EFS) of the patients. EFS and overall survival (OS) data will be compared within this single arm study to non-vaccinated patients of a historic control cohort. Patients will be recruited through the Society for Pediatric Oncology/Hematology (GPOH) networks Cooperative Soft Tissue Sarcoma Group (CWS) and Cooperative Ewing Sarcoma Group (CESS) and through the "Deutsches Konsortium für Translationale Krebsforschung" (DKTK) programs MASTER and INFORM as well as HEROES-AYA. For the screening phase, n=30 patients will be recruited, n=23 patients should be treated with at least one vaccine dose, with a drop-out rate we need n=21 patients for sufficient statistical power. Primary objective is to evaluate the safety, toxicity and in vivo immunological effects of a patient-individualized peptide vaccination (IPX vaccine) in patients with primary or relapsed metastasized fusion-driven sarcoma (FDS, rhabdomyosarcoma, Ewing- and synovial sarcoma) with an age ≥ 2 to \< 40 years in first or second complete remission or stable partial remission. Primary endpoint is "success of treatment", defined as the patient showing a vaccination-induced T cell response without unacceptable toxicity until Follow-up visit (28 ± 7 days after last vaccination).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Peptide vaccine is a combination of 1. class II peptide spanning the sarcoma-specific fusion-breakpoint (fusion-peptide) 2. class-II neopeptide based on a patient-individual nonsynonymous mutation with a high immunogenicity (mutation-based neopeptide). 3. control peptide derived from Survivin. 4. adjuvant: toll like receptor (TLR) 1/2 ligand XS15.
Pediatrics III, West German Cancer Centre, University Hospital
Essen, Germany
NOT_YET_RECRUITINGUniversitätsklinikum, Klinik für Kinder- und Jugendmedizin
Frankfurt am Main, Germany
NOT_YET_RECRUITINGZentrum für Kinder- und Jugendmedizin, Universitätsklinikum
Freiburg im Breisgau, Germany
NOT_YET_RECRUITINGUniversity Children's Hostpital
Tübingen, Germany
RECRUITINGSuccess of treatment
The primary composite safety/efficacy outcome of "treatment success" is defined as number of patients 1. without unacceptable toxicity (any toxicity \> grade 3 according to NCI-CTC) until Follow-up visit (28 ± 7 days after last vaccination) and 2. with vaccination-induced response of cluster of differentiation 4+ (CD4+) and/or cluster of differentiation 8+ (CD8+) T cells to the patient-specific peptides at Follow-up visit (28 ± 7 days after last vaccination). CD4+ and CD8+ T cells will be measured by flow cytometry.
Time frame: Follow-up visit at 28 +/- 7 days after last vaccination
T-cell response at follow up
Number of patients with 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).
Time frame: Beginning of trial phase until follow-up visit at 28 +/- 7 days after last vaccination
T-cell response at final follow up
Number of patients with 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).
Time frame: Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination
Event free survival
Rate of patients that survived without progression according to RECIST criteria, stratified for immune response yes/no
Time frame: Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination
Overall survival
Rate of patients that survived. stratified for immune response yes/no
Time frame: Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination
Quality of life (QoL) defined as overall quality of life in children
QoL (Quality of life) is defined as overall quality of life measured by Pediatric Quality of Life InventoryTM PedsQL (4.0). The PedsQL uses a 0 to 4 scale with 0=never and 4=almost always.
Time frame: Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination
Quality of life (QoL) defined as overall quality of life in adults
QoL (Quality of life) is defined as overall quality of life measured by European Organisation for Research and Treatment of Cancer EORTC quality of life questionnaire (QLQ) C-30 (3.0). EORTC QLQ C-30 uses a 1-4 scale with 1=not at all and 4=very much and a 1-7 scale with 1=very poor and 7=excellent.
Time frame: Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination
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