Phase II Trial of Vaccination with Lysate-loaded, Mature Dendritic Cells Integrated Into Standard Radiochemotherapy in Newly Diagnosed Glioblastoma
Overview
- Phase
- Phase 2
- Intervention
- Autologous, tumor lysate-loaded, mature dendritic cells (DC)
- Conditions
- Glioblastoma
- Sponsor
- Heinrich-Heine University, Duesseldorf
- Enrollment
- 136
- Locations
- 6
- Primary Endpoint
- Overall survival (OS)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
The primary objective of the study is to determine whether overall survival of newly diagnosed glioblastoma patients treated with lysate-loaded, mature dendritic cell vaccines as add-on to the standard of care consisting of resection, radiotherapy with concomitant temozolomide chemotherapy and subsequent adjuvant temozolomide chemotherapy is superior to the treatment with the standard of care alone.
Detailed Description
This is a multicenter, randomized, phase 2 study, integrating vaccination with tumorlysate-loaded mature dendritic cells into standard radio/temozolomide-chemotherapy of newly diagnosed glioblastoma patients with near-complete resection after fluorescence-guided resection. Only patients with confirmed gross-total resection and a residual tumor volume below 5 ml will be eligible for the trial. Vaccination will be performed after radio- and concomitant temozolomide chemotherapy and during the first three cycles of adjuvant TMZ.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Determined at pre-screening (prior to surgery; wk-3 - wk-1):
- •Patients ≥ 18 years of age at surgery.
- •Patients must be in a cognitive state to understand and sign the informed consent indicating that they are aware of the investigational nature and procedures of the study.
- •First written informed consent for screening for eligibility, including tumor tissue collection, transfer and processing, central neuropathological evaluation of Tumor sample, central neuroradiological assessment of extent of resection, infectious disease (HIV, HBV, HCV, Treponema pallidum) testing, determination of MGMT promoter methylation status and pregnancy testing.
- •Determined at screening (at and post-surgery; d0 - wk3):
- •Newly diagnosed, monofocal GBM, IDH wildtype (WHO grade IV), including the histological variants of gliosarcoma and giant cell glioblastoma, confirmed by central neuropathologist according to the WHO classification of central nervous System tumors
- •Tumors may cross into, but not beyond the corpus callosum.
- •Near-complete resection (≤ 5 ml residual contrast enhancing tumor volume) confirmed by central neuroradiologist on MRI scan within 72 h postoperative; awake surgery and second look surgery are possible, if medically indicated.
- •Sterile tumor sample of ≥ 150 mg with tumor cell frequency ≥ 60% as determined by central neuropathologist available for vaccine production.
- •Successful production of sterile, avital tumor lysate.
Exclusion Criteria
- •determined at pre-screening (prior to surgery; wk-3 - wk-1):
- •Medical history of severe acute or chronic disease with poor prognosis, e.g. severe coronary heart disease, heart failure (New York Heart Association classes III/IV), severe poorly controlled diabetes, severe mental retardation or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
- •Medical history of severe autoimmune disorder or immunodeficiency or patients with organ allograft.
- •Medical history of bleeding diathesis or coagulopathy.
- •Prior malignancy during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with prostate-specific antigen (PSA) level less than ULN.
- •Previous radiotherapy to head and neck.
- •Known allergy or intolerability to TMZ, dacarbazine, the contrast agent or to components of the dendritic cell vaccine.
- •Current treatment of glioblastoma in another clinical trial with therapeutic intervention or current use of any other investigational agent.
- •Known pregnancy or breast feeding.
- •No known severe infection requiring treatment.
Arms & Interventions
Experimental intervention
Fluorescence-guided surgery (day 0) Leukapheresis (wk4) Fractionated radiotherapy (60 Gy: 2 Gy/d, 5/7 d, 6 wks; wk5 10) and concomitant TMZ chemotherapy (75 mg/m2/d; 6 wks; wk5-10) vaccination with autologous, tumor lysate-loaded, mature dendritic cells (DC) (7x, 2 - 10 x 106 DC each, intradermal injection, weekly wk11-14, wk17, 21, 25)Adjuvant TMZ chemotherapy (150-200 mg/m2/d, 6x, days 1 5 of 28 d cycle: wk15, 19, 23, 27, 31, 35)
Intervention: Autologous, tumor lysate-loaded, mature dendritic cells (DC)
Control intervention
Standard therapy: Fluorescence-guided surgery (day 0) Fractionated radiotherapy (60 Gy: 2 Gy/d, 5/7 d, 6 wks; wk5 10) and concomitant TMZ chemotherapy (75 mg/m2/d; 6 wks; wk5-10) Adjuvant TMZ chemotherapy (150-200 mg/m2/d, 6x, days 1 5 of 28 d cycle: wk15, 19, 23, 27, 31, 35)
Intervention: standard therapy
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: Day of surgery until death of any cause assessed up to 34 months
Overall survival as measured from the day of surgery until death from any cause assessed up to 34 months
Secondary Outcomes
- Quality of life of cancer patients(34 months)
- Progression free survival (PFS)(Day of surgery until day of diagnosis of tumor progression assessed upto 34 months)
- OS rates(6, 12 and 24 months after the day of surgery)
- PFS rates(6, 12 and 24 months after the day of surgery)
- Frequency and severity of adverse events(34 months)
- Karnofsky Performance Status(34 months)
- MMSE-2(34 months)
- Psychological distress in oncology patients(34 months)
- Quality of life in patients with brain cancer(34 months)
- Psychological distress, anxiety and depression(34months)