Trial Title:
Personalized Vaccination in Fusion+ Sarcoma Patients (PerVision)
NCT ID:
NCT06094101
Condition:
Ewing Sarcoma
Rhabdomyosarcoma
Synovial Sarcoma
Conditions: Official terms:
Sarcoma
Rhabdomyosarcoma
Sarcoma, Ewing
Sarcoma, Synovial
Conditions: Keywords:
metastasized fusion-driven sarcoma
clinical study
phase I/II
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
interventional, multicenter, open-label, phase I/II feasibility and early proof of
concept study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Peptide vaccine IPX
Description:
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.
Arm group label:
Peptide vaccination
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.
Detailed description:
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria, definition of partial remission plus (PRplus)
- 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.
Exclusion Criteria:
- 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.
- Male subjects of reproductive capacity not agreeing to use effective contraception
from first vaccination of this study to 180 days after the last vaccination.
- Not willing and/or not able to comply with treatment plan, scheduled visits,
laboratory tests, contraceptive guidelines and other study procedures.
- History of any illness or clinical condition that might confound the results of the
study or pose an additional risk in administering study drug to the subject,
according to the judgement of the investigator. This may include but is not limited
to: history of central nervous system or cardiovascular disease, history of relevant
drug allergies, history of psychiatric disorder, history or present of clinically
significant pathology.
- Karnofsky performance status of < 70% for subjects ≥ 16 years of age, Lansky
performance status of < 70% for subjects < 16 years of age
- Participation or intended participation in another clinical phase I or II trial with
an investigational drug or product within 28 days prior to enrollment (with the
exception to participation of the "frontline and relapsed rhabdomyosarcoma study"(
(FaR-RMS) after completion of the maintenance therapy (EudraCT-2018-000515-24)).
Commonly used drugs as per standard or phase III-trials are permitted.
Gender:
All
Minimum age:
2 Years
Maximum age:
40 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Pediatrics III, West German Cancer Centre, University Hospital
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Uta Dirksen, Prof.
Phone:
0049.201.7238084
Email:
uta.dirksen@uk-essen.de
Contact backup:
Last name:
Dirk Reinhardt
Phone:
0049-201-7233784
Email:
dirk.reinhardt@uk-essen.de
Facility:
Name:
Universitätsklinikum, Klinik für Kinder- und Jugendmedizin
Address:
City:
Frankfurt am Main
Zip:
60590
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Konrad Bochennek, Dr.
Phone:
+49 69 6301-5243
Contact backup:
Last name:
Eva Rettinger, Dr.
Phone:
+49 69 6301-5040
Facility:
Name:
Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum
Address:
City:
Freiburg
Zip:
79106
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Simone Hettmer, Prof. Dr.
Phone:
+49 761 27043000
Email:
simone.hettmer@uniklinik-freiburg.de
Contact backup:
Last name:
Christian Flotho, Prof. Dr.
Phone:
+49 761 27046280
Email:
christian.flotho@uniklinik-freiburg.de
Facility:
Name:
University Children's Hostpital
Address:
City:
Tübingen
Zip:
72076
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Martin Ebinger, Prof. Dr.
Phone:
+49 7071 2983781
Email:
martin.ebinger@med.uni-tuebingen.de
Contact backup:
Last name:
Joachim Rupprecht, Dr.
Email:
joachim.rupprecht@med.uni-tuebingen.de
Start date:
September 19, 2023
Completion date:
September 2027
Lead sponsor:
Agency:
University Hospital Tuebingen
Agency class:
Other
Collaborator:
Agency:
Deutsches Konsortium fürTranslationale Krebsforschung (DKTK)
Agency class:
Other
Collaborator:
Agency:
Cooperative Ewing Sarkom Studiengruppe
Agency class:
Other
Collaborator:
Agency:
Cooperative Weichteilsarkom Study Group
Agency class:
Other
Source:
University Hospital Tuebingen
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06094101
