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임상시험 NCT07347210 (MATVAC-1)은(는) 원발성 교모세포종에 대해 대상자모집전 상태입니다. 모든 세부 정보를 보려면 임상시험 레이더 카드 뷰와 AI 발견 도구를 확인하거나 여기에서 무엇이든 물어보세요. | ||
Evaluation of UCPVax Vaccine +/- Pembrolizumab Combined With Standard Treatment as Adjuvant Therapy in Patients With Unmethylated MGMT Glioblastoma (MATVAC-1) 2상 98 면역 요법 백신 전체 생존기간 번역 제공
Evaluation of UCPVax Vaccine +/- Pembrolizumab Combined With Standard Treatment as Adjuvant Therapy in Patients With Unmethylated MGMT Glioblastoma: a Randomized Phase II Trial
- MATVAC-1
- 2024/894
- 2024-514399-42-00 (EU 시험 (CTIS) 번호)
UCPVax
pembrolizumab
cancer vaccine
telomerase
CD4 T cell
| 참가자 그룹/시험군 | 개입/치료 |
|---|---|
실험적Experimental Arm A UCPVax + Pembrolizumab + Standard of care | UCPVax Priming : UCPVax (two helper peptides UCP2 and UCP4 + Montanide ISA51) at 0.5 mg subcutaneously at day 1, 8, 15, 29, 36 and 43
Boost : UCPVax at 0.5 mg subcutaneously one month after priming and then every 8 weeks for 12 months maximum Pembrolizumab 400 mg/m1 every 6 weeks since day 1 until disease progression or unacceptable toxicity for a maximum of 1 year 테모졸로마이드 150-200 mg/m2/day x 5 days per month x 6 months according to best standard of care starting at day 1 of week 1 (with vaccine 1 of UCPVax).
Additional treatment with NOVO-TTF200A will be allowed. |
실험적Experimental Arm B UCPVax + Standard of care | UCPVax Priming : UCPVax (two helper peptides UCP2 and UCP4 + Montanide ISA51) at 0.5 mg subcutaneously at day 1, 8, 15, 29, 36 and 43
Boost : UCPVax at 0.5 mg subcutaneously one month after priming and then every 8 weeks for 12 months maximum 테모졸로마이드 150-200 mg/m2/day x 5 days per month x 6 months according to best standard of care starting at day 1 of week 1 (with vaccine 1 of UCPVax).
Additional treatment with NOVO-TTF200A will be allowed. |
기타Control Arm C Standard of care | 테모졸로마이드 150-200 mg/m2/day x 5 days per month x 6 months according to best standard of care starting at day 1 of week 1 (with vaccine 1 of UCPVax).
Additional treatment with NOVO-TTF200A will be allowed. |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
Assessment of the Overall Survival (OS) at 18 months since randomization of patients with GBM treated in the experimental arm with UCPVax +/- pembrolizumab combined with standard treatment (Temozolomide +/- Novo-TTF-200A) | Rate for patients alive at 18 months post-randomization | 18 months |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
Assessment of the Overall Survival (OS) at 18 months since randomization of patients with GBM treated in the control arm receiving standard treatment( Temozolomide +/- NovoTTF-200A) | The rate of patients alive at 18 months post randomization | 18 months |
Assessment of the Overall Survival (OS) in the three arms | Overall survival (OS) defined as the time interval from randomization to the date of death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period | from date of randomization until date of death from any cause, assessed up to 42 months |
Assessment of the progression free survival (PFS) since randomization in the three arms | Progression free survival (PFS) according to RANO 2.0 criteria: defined as the time interval from the date of randomization to the date of first documented disease progression or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation showing no progression during study treatment follow-up. | From date of randomization until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 42 months |
Assessment of the progression free survival (PFS) at 6 months since randomization in the three arms | Progression free survival (PFS) according to RANO 2.0 criteria: defined as the time interval from the date of randomization to the date of first documented disease progression or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation showing no progression during study treatment follow-up. | 6 months |
Evaluation of incidence of treatment-emergent adverse events in the three arms | Adverse events and routine lab abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness and relationship to study treatments at each visit. | up to 42 months |
Assessment of the immunogenicity of the proposal combination therapy. | UCP specific TCD4 T-cell response will be assess by ex vivo IFN-γ ELISpot in peripheral blood (Adotevi JCO 2023). | average of 30 months |
Evaluation of health-related quality of life (HrQoL) in the two arms | Health related Quality of life will be evaluated with EORTC-QLQC30 questionnaire and BN20 module at randomization and at 6 months. | up to 42 months |
Exploratory biomarker study | average of 30 months |
Male or female, age ≥ 18 with informed consent signed
Patient with a confirmed histological diagnosis of non-mutated IDH primary glioblastoma (surgical resection or biopsy).
Tumor with unmethylated MGMT promoter status
Patients having completed the concomitant phase of radiotherapy + temozolomide regimen (standard radiotherapy with 60 Gy in 30 fractions or hypofractionated radiotherapy with 40 Gy in 15 fractions), and eligible for the 6 monthly cycles of maintenance temozolomide
Karnofsky Perfomance status (KPS) ≥ 70%
Life expectancy ≥ 3 months
If patient is treated by corticosteroïds (CS), patient must be on stable CS dose for 15 days and total daily dose ≤ 10 mg prednisone, or equivalent
Adequate organ function laboratory values
Females must be using highly effective contraceptive measures, and have a negative pregnancy test prior to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening :
- Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
- Women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution.
- Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but tubal ligation.
Female with childbearing potential must use effective contraception during study treatment and after the end of treatment based on the last study drug administrated: 6 months after the last dose of Temozolomide; 4 months after the last dose of pembrolizumab and 1 month after the last injection of UCPVax.
Male patients with a female partner of childbearing potential should be willing to use barrier contraception and to refrain from donating sperm during the study and and post-treatment based on the last study drug administrated: 3 months after the last dose of temozolomide; 4 months after the last pembrolizumab dose; 1 month after the last UCPVax injection.
Patient affiliated to or beneficiary of French social security system
Ability to comply with the study protocol, in the Investigator's judgment.
Signed and dates informed consent
Patients will not be eligible for this study for any of the following reasons:
Cancer specific exclusion criteria:
IDH1 or IDH2 mutated tumor
Presence of extracranial metastasis
Leptomeningeal disease on MRI
Contrast enhancement ≥4 cm (largest diameter on axial T1 sequences) on inclusion MRI
Previous treatment with Carmustine impregnated wafers (GliadelR)
Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists
Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study.
Non-eligible to treatment by UCPVax:
Prior therapy with an anti-PD-1, anti-PD-L1, or with an agent directed to another immune checkpoint (e.g. CTLA-4, TIGIT, Lag3…).
Immunosuppressive treatment including CS > 10 mg prednisone or equivalent within the previous 2 weeks
Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
Has a known history of Human Immunodeficiency Virus (HIV) infection.
History of tuberculosis infection
History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Active auto-immune disease that has required a systemic treatment in the past 2 years (i.e. corticosteroïds or immunosuppressors). Replacement therapy (e.g. thyroxine, insulin) is allowed.
Active or history of auto-immune disease or immune deficiency
History of solid organ transplant nor allogenic hematopoietic stem cell transplantation
Hypersensitivity to the active substance temozolomide or to any of the excipients listed (anhydrous lactose, colloidal anhydrous silica, sodium carboxymethyl starch type A, tartaric acid, stearic acid),
Hypersensitivity to dacarbazine (DTIC)
Hypersensitivity to the active substance pembrolizumab or to any of the excipients listed (L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80 (E433))
Hypersensitivity to the active substance Montanide
Uncontrolled active systemic fungal, bacterial, viral, or other infection within the previous 4 weeks or requirement for intravenous (IV) antibiotics within the last two weeks
Inadequate hematology and organ functions; known cardiac failure or unstable coronaropathy, respiratory failure or another life threatening condition.
Patient with unresolved non-hematologic toxicities > Grade 1 (or > Grade 2 if deemed acceptable by the investigator and not considered a safety risk)
Major surgery within 1 month prior randomization or planned during the study
Vaccination with alive attenuated vaccine within 4 weeks prior the first dosing. Patient must agree not to receive live attenuated vaccine including influenza vaccine during the treatment and within 6 months following the last dose of pembrolizumab
Non-eligible to a clinical trial:
Diagnosis of another malignant tumor within 2 years before randomization except treating resected basocellular carcinoma and carcinoma in situ such as breast cancer, endometrial or cervical carcinoma that have undergone curative therapy.
Current or treatment with another investigational drug within the previous 4 weeks.
Breast-feeding or pregnant women, no effective contraception if risk of conception exists (up to 4 months after end of chemotherapy)
Centre Hospitalier Universitaire de Besancon머크