PERVI-FUS|PERVI-NEO|11902A for Ewing sarcoma | Alveolar rhabdomyosarcoma | Synovial sarcoma

Inclusion criteria

• {"criterion_text":"- Confirmed metastatic fusion-driven rhabdomyo-, Ewing- and synovial sarcoma in complete remission (CR) or partial response (PR) after local therapy and intensive standard chemotherapy protocols.\n- Whole exome sequencing and RNAseq 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 Version 2.0 19.06.2023 Seite 29 von 95 for Tumor Eradication) or HEROES-AYA networks (Heterogeneity, evolution and resistance of fusion-driven sarcomas in AYA) or similar evaluation\n- Design and production of the patient-individual vaccine cocktail was successful\n- 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 remissionplus 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

• {"criterion_text":"- Age < 2 or > 40 years (only stage 1)\n- 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\n- Current or anticipated need for any of the following medications interfering with T cell function from 30 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).\n- Significant psychiatric disabilities that, in the judgment of the investigator, do not assure reliable participation in the present study.\n- Uncontrolled seizure disorders (occurrence of at least one generalized seizure in the last 3 months) or severe peripheral neuropathy/leukencephalopathy (> grade 2 according to NCI CTCAE v5.0 neurotoxicity criteria).\n- Autoimmune disease (e.g. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, autoimmune dermatitis) requiring immunosuppressive treatment. Less acute autoimmune diseases like diabetes mellitus type 1, Vitiligo and Hashimoto-Thyreoiditis not requiring immunosuppressive therapy are no exclusion criteria.\n- Pregnant females\n- 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.\n- Male subjects of reproductive capacity not agreeing to use effective contraception from first vaccination of this study to 180 days after the last vaccination.\n- Not willing and/or not able to comply with treatment plan, scheduled visits, laboratory tests, contraceptive guidelines and other study procedures\n- 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.\n- Ejection fraction < 25%\n- Karnofsky performance status of < 70% for subjects ≥ 16 years of age, Lansky performance status of < 70% for subjects < 16 years of age\n- 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 FaR-RMS study after completion of the maintenance therapy (EudraCT-2018-000515-24)). Commonly used drugs as per standard or phase III-trials are permitted.\n- Creatinine-clearance < 40ml/min\n- Bilirubin > 4mg/dl\n- ALT > 400U/l and/or AST > 400U/l\n- 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 antibody [HCAb] or for NAT test. Other infections that, in the opinion of the investigator, do not allow a participation in the study.)\n- Subjects with a known hypersensitivity / allergy to any component of the study drugs\n- Subjects who have received a live, attenuated vaccine within 28 days prior to the administration of the study drug (only stage 2).\n- Subjects with a prior allogenic haematopoietic stem cell transplantation / prior organ transplantation."}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Defined as patient showing a vaccination-induced T cell response to either of the two patient-specific peptides and absence of unacceptable toxicity until follow-up visit (28 ±7 days after last vaccination)."}

Secondary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Measurement: CD8+ and/or CD4+ T-cell responses measured as ≥2-fold above background in response to either patient-specific peptides."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measurement at day 180: CD8+ and/or CD4+ T-cell responses measured as ≥2-fold above background in response to either patient-specific peptides."}
• {"endpoint_text":"- C) Event-free (EFS) at day 180.","definition_or_measurement_approach":"Event-free survival assessed at day 180."}
• {"endpoint_text":"- D) Overall survival (OS) at day 180","definition_or_measurement_approach":"Overall survival assessed at day 180."}
• {"endpoint_text":"- E) Quality of life during study treatment.","definition_or_measurement_approach":"Quality of life assessed during study treatment (method not specified in provided record)."}

Germany

Earliest CTIS Part Ii Submission Date

03-10-2024

Latest Decision Or Authorization Date

11-11-2025

Processing Time Days

404

Number Of Sites

7

Number Of Participants

23

Primary sponsor

Full Name

Universitaetsklinikum Tuebingen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany