Personalized Vaccination in Fusion+ Sarcoma Patients (PerVision)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age2-40
SponsorUniversity Hospital Tuebingen
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Confirmed metastatic fusion-driven rhabdomyosarcoma, Ewing- and synovial sarcoma in first or second complete remission (CR) or partial response (PR) after local therapy and intensive standard chemotherapy protocols.
Whole exome sequencing and RNA sequencing data of the gene fusion (fusion-breakpoint RNA sequence) must be available by registration to the INFORM (Individualized therapy for relapsed malignancies in childhood), MASTER (Register study Molecularly Aided Stratification for Tumor Eradication) or HEROES-AYA networks (Heterogeneity, evolution and resistance of fusion-driven sarcomas in AYA) or similar evaluation.
Design and production of the patient-individual vaccine cocktail was successful
Patients have reached a complete or stable partial remission (CR or PR) the end of adjuvant and/or maintenance cytotoxic treatment. Cytotoxic treatment as per standard or trial recommendations has been completed. Definition of PRplus: Partial remission(plus) implicates that all remaining tumor residua including all metastases have received local therapy by this time point: Either surgical removal or local irradiation. The assessment of which therapy modality and, in the case of irradiation, which radiation dose is selected, lies with the treating physician. Whether PRplus is achieved will be decided finally by the investigator after review of the patient records.
Disqualifiers
Ejection fraction < 25%
Creatinine-clearance < 40ml/min
Bilirubin > 4mg/dl
Alanine aminotransferase (ALT) > 400 units (U)/l and/or aspartate aminotransferase (AST) > 400 U/l
Trial design
Design model
Single group
Treatments tested in this trial
Peptide vaccine IPX
Biological/VaccinePeptide 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.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Peptide vaccinationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Success 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 vaccinationSecondary outcomes
1
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 vaccination2
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 vaccination3
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 vaccination4
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 vaccinationSponsors and contacts
Click on the lead sponsor to view all of their trials.
University Hospital Tuebingen
Lead sponsor
Deutsches Konsortium fürTranslationale Krebsforschung (DKTK)
Collaborator
Cooperative Ewing Sarkom Studiengruppe
Collaborator
Cooperative Weichteilsarkom Study Group
Collaborator
Source ClinicalTrials.gov