Personalized Vaccination in Fusion+ Sarcoma Patients (PerVision)

NCT06094101 | Recruiting Phase 1 DMC

• 1 other identifier: 2022-002793-91
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma

Keywords

metastasized fusion-driven sarcoma; clinical study; phase I/II

Outcome Measures

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.

  Follow-up visit at 28 +/- 7 days after last vaccination

Secondary Outcomes (6)

• T-cell response at follow up

  Beginning of trial phase until follow-up visit at 28 +/- 7 days after last vaccination

• T-cell response at final follow up

  Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination

• Event free survival

  Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination

• Overall survival

  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

  Beginning of trial phase until final follow-up at 120 +/- 14 days after last vaccination

Study Arms (1)

Peptide vaccination

EXPERIMENTAL

Peptides will be administered subcutaneously (s.c.) together with the novel toll like receptor (TLR) 1/2 ligand XS15 emulsified in Montanide ISA 51 VG as adjuvant. Three vaccinations will be applied every 28 days.

Biological: Peptide vaccine IPX

Interventions

Peptide vaccine IPX BIOLOGICAL

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.

Peptide vaccination

Eligibility Criteria

• Age: 2 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Screening Stage 1:
• 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.
• Screening stage 2:
• 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.

You may not qualify if:

• 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
• Severe infection (Human immunodeficiency virus (HIV): positive for the presence of human immunodeficiency virus-1 or human immunodeficiency virus-2 (positive antigen/antibody or nucleic acid tests \[NAT\]) and CD4-positive cells \< 500/μl. Hepatitis B virus: positive for the presence of hepatitis B virus (positive for hepatitis B core antibody \[HBcAb\] or positive hepatitis B surface antigen \[HBsAg\]) and hepatitis B NAT test \> 2000 IU/ml). Hepatitis C virus: positive for heavy chain only antibody \[HCAb\] or for nucleic acid amplification testing (NAT). Other infections that, in the opinion of the investigator, do not allow a participation in the study.)
• Subjects with a known hypersensitivity / allergy to any component of the study drugs.
• Subjects who have received a live, attenuated vaccine within 28 days prior to the administration of the study drug (only stage 2).
• Subjects with a prior haematopoietic stem cell transplantation / prior organ transplantation.
• Patients suffering from other malignancies (with the exception of those with a negligible risk of metastasis or death and treated with curative outcome) within 5 years prior to study start.
• Current or anticipated need for any of the following medications interfering with T cell function from 14 days before 1st vaccination until 28 days after 1st vaccination: Immunosuppressive agents, which influence functionality and activity of T cells, such as steroids (more than 0,5 mg/kg body weight prednisolone-equivalent), calcineurin-inhibitors, mofetil mycophenolate, sirolimus, everolimus, and cytotoxic medication. Those drugs should be avoided until 28 days after third/final vaccination but may be given after discussion with the principal investigator. Application of tyrosine kinase inhibitors is permitted during the trial (only stage 2).
• Significant psychiatric disabilities that, in the judgment of the investigator, do not assure reliable participation in the present study.
• Uncontrolled seizure disorders (occurrence of at least one generalized seizure in the last 3 months) or severe peripheral neuropathy/leucoencephalopathy (\> grade 2 according to NCI CTCAE v5.0 neurotoxicity criteria).
• Autoimmune disease (e.g. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, autoimmune dermatitis) requiring immunosuppressive treatment
• Pregnant females
• Female subjects of childbearing potential (postmenarcheal, with an intact uterus and at least one ovary, and less than one year postmenopausal) not agreeing to use acceptable method(s) of contraception from 30 days prior to Screening stage 2 visit to 180 days after the last vaccination.

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• Deutsches Konsortium fürTranslationale Krebsforschung (DKTK): collaborator
• Cooperative Ewing Sarkom Studiengruppe: collaborator
• Cooperative Weichteilsarkom Study Group: collaborator

Study Sites (4)

Pediatrics III, West German Cancer Centre, University Hospital

Essen, 45147, Germany

NOT YET RECRUITING

Universitätsklinikum, Klinik für Kinder- und Jugendmedizin

Frankfurt am Main, 60590, Germany

NOT YET RECRUITING

Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum

Freiburg im Breisgau, 79106, Germany

NOT YET RECRUITING

University Children's Hostpital

Tübingen, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Sarcoma, Ewing; Rhabdomyosarcoma; Sarcoma, Synovial

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Myosarcoma; Neoplasms, Muscle Tissue

Study Officials

• Martin Ebinger, Prof. Dr.

  University children's hospital Tübingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Ebinger, Prof. Dr.

CONTACT

+49 7071 2983781; martin.ebinger@med.uni-tuebingen.de

Joachim Rupprecht, Dr.

CONTACT

joachim.rupprecht@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: interventional, multicenter, open-label, phase I/II feasibility and early proof of concept study

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 23, 2023
• Study Start: September 19, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)