Spots Global Cancer Trial Database for Immunotherapy With Autologous Tumor Lysate-Loaded Dendritic Cells In Patients With Newly Diagnosed Glioblastoma Multiforme

Study Description

Brief Summary: Rationale of the Study: Treatment for GBM currently consists of surgical resection of the tumour mass followed by radio- and chemotherapy ((1)Stupp et al., 2005). Nonetheless overall prognosis still remains bleak, recurrence is universal, and recurrent GBM patients clearly need innovative therapies. Dendritic cells (DC) immunotherapy could represent a well-tolerated, long-term tumour-specific treatment to kill all (residual) tumour cells which infiltrate in the adjacent areas of the brain. Preclinical investigations for the development of therapeutic vaccines against high grade gliomas, based on the use of DC loaded with a mixture of glioma-derived tumor have been carried out in rat as well as in mouse models, showing the capacity to generate a glioma-specific immune response. Mature DC loaded with autologous tumor lysate have been used also for the treatment of patients with recurrent malignant brain tumors; no major adverse events have been registered. Results about the use of immunotherapy for GBM patients are encouraging, but further studies are necessary to find out the most effective and safe combination of immunotherapy with radio- and chemotherapy after exeresis of the tumour mass. Aim of the study. Primary objective of the study is to evaluate treatment tolerability and to get preliminary information about efficacy. Secondary objective is to evaluate the treatment effect on the immune response. Additional objective is to identify a possible correlation between methylation status of MGMT promoter and tumor response to treatment. A two-stage Simon design ((2)Simon, 1989) will be considered for the study. Assuming as outcome measure the percentage of PFS12 patients and of clinical interest an increase to 42% (P1) of the historical control rate of 27% (P0) ((1)Stupp et al., 2005), the alternative hypothesis will be rejected at the end of the first stage if the PFS12 rate will be less than 8/24 treated patients (Fisher's exact test). In the second stage patients will be enrolled up to 76 overall. The null hypothesis will be rejected (a=0.05, b=0.2) if at least 27 subjects out of 76 are alive and progression free 12 months after the beginning of the treatment.

Detailed Description: Background and significance. The therapeutic program will include radical surgical resection of the tumor, followed by radiotherapy (fractionated local field irradiation in daily fractions of 2 Gy given 5 days per week, Monday through Friday for 6 weeks, for a total of 60 Gy) plus temozolomide (TMZ) chemotherapy (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy). After a 4-week break, up to 6 cycles of maintenance TMZ (mTMZ) will be administered according to the standard 5-day (oral intake) schedule every 28 days. TMZ dose will be 150 mg per square meter for the first cycle and will be increased to 200 mg per square meter beginning with the second cycle, so long as there is no hematologic toxic effect. Immunotherapy will follow radiochemotherapy and will comprise 4 vaccinations every second week (injections I, II, III, IV), 2 further monthly vaccinations (injections V, VI) and a final vaccination (injection VII) 2 months after the sixth one. Injections I, V, VI and VII will contain 10 million tumor lysate-loaded DC, while the others will be of 5 million cells only. In correspondence to the third vaccine injection (week 13), mTMZ will start. On the basis of the patient clinical status, further vaccine boosts will be considered as appropriate addition at the standard vaccination cycle.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

Useful links and downloads for this trial