Glioblastoma is the most common primary brain tumour in humans with the most severe prognosis. Standard treatments consist primarily of surgery in order to debulk thetumoral mass, as well as radiochemotherapy to induce optimal local tumor control. However the median overall survival (OS)is about 15 months, with 88% of patients dead within 3 years MedDRA version: 18.0 Level: HLT Classification code 10045172 Term: Tumour vaccine therapies System Organ Class: 100000004865
Conditions
Interventions
Trade Name: DPX-SURVIVAC
Product Name: DPX-Survivac
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DPX-SURVIVAC
Other descriptive name: SURVIVAC
Concentration unit: ml millilitre(s)
Sponsors
Sapienza, University of Rome
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Primary or recurrent histologically confirmed GBM after surgery 2.Total or subtotal (at least 90%) resection of tumour mass, confirmed by assessment of neurosurgeon and postoperative magnetic resonance imaging (MRI) within 48 hours 3.Ages 18 to 70 years old 4.Postoperative Karnofsky Performance Status (KPS) =70 5.A life expectancy > 6 months 6.Adequate hematologic, renal and hepatic function 7.Fertile subjects must use acceptable birth control from screening until the last study visit or early termination. Acceptable methods of birth control include: spermicide with condom, diaphragm, or cervical cap, IUD (intrauterine device), hormonal contraception, vasectomy, and abstinence. (Plan B or the rhythm method are not considered reliable methods.) 8.Willing and able to provide written informed 9.Ability to comply with protocol requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1.Past or ongoing documented autoimmune diseases 2.HIV, syphilis, active HBV and HCV infection 3.Any medical disorder that would impair the ability to receive study treatment 4.Other active of in the past five years malignancies 5.Any unresolved chronic toxicity greater than Grade 2 (NCI-CTCAE version 4.03) from previous anticancer therapy (except alopecia) 6.Pregnant or breast feeding patients 7.Documented immune deficiency 8.Lymphodemia in the region to be vaccinated 9. Mandatory treatment with corticosteroids or salicylates in inflammatory dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The rationale of this study is to investigate the efficiency of survivin vaccines (with adjuvant ) to stimulate specific anti tumor immunity and decrease immunosuppression in GBM patients and potentially affect overall survivall and to assess the need of the addition of cyclophoshamide for the optimal immune activation. Primary endpoint is the activation of the immune response in vaccinated patients. A 2-fold increase of specific T cells activation will be considered positive. ;Secondary Objective: Increase of OS and PFS (secondary endpoints) in GBM patients treated with gold standard after the administration of Depovax alone or in association with a metronomic dose of Cyclophosphamide. To assess the safety profile of subcutaneous administration of DPX Survivac alone or with low dose oral cyclophosphamide ;Primary end point(s): The activation of the immune response in vaccinated patients as primary endpoint will be considered postive with a value corresponding to a 2-fold increase of specific T cells activation. The parameters evaluated will be: •Specific populations of CD4+ and CD8+ T Lymphocytes activated by survivin (primary endpoint) •Modulation of immunosuppressive cellular populations (Tregs, TAM-M2, MDSC) •Epitope spreading phenomenon vaccine-induced (against tumor lysate or others TAAs) •Immunogenic death, evaluated by specific markers such as Calreticulin, HSP70,90 and HMGB1. Immune system will be investigated for the following readout: 1. Determine if standard therapies performed in conjunction with vaccination increase immune activation; 2. Define if standard treatments with or without survivin vaccination can be effective in reducing immunosuppression (Tregs); 3. Identify biological markers to monitor response to therapy and disease progression; 4. Define the optimal vaccination schedule according to the immunological status of patient. ;Timepoint(s) of evaluation of this end point: A venous blood sample (50ml) will be collected fr | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Increase of OS and PFS (secondary endpoints) in GBM patients treated with gold standard (Stupp, NEJM 2005) after the administration of Depovax alone or in association with a metronomic dose of Cyclophosphamide. To assess the safety profile of subcutaneous administration of DPX Survivac alone or with low dose oral cyclophosphamide ;Timepoint(s) of evaluation of this end point: Timepoints of evaluation of OS (overall survival) and PFS (progression free survival) will be investigated during the follow up at the time: - one month after treatment end. - three months after treatment end. - six months after treatment end. - nine months after treatment end. - twelve months after treatment end. | — |
Countries
Italy
Contacts
Public ContactMarianna Nuti
Sapienza, University of Rome
Outcome results
None listed