This study is founded by MUSC Foundation. The purpose of this study is to determine the correlation between genetic and neuroimaging of a human brain tumors, specifically a type of tumor called glioblastoma (GBM). This study will also study the signature and prognosis of GBM.
This is an international, multicenter, double-blind clinical trial of rindopepimut. This research study is sponsored by Celldex Therapeutics, Inc. The purpose of this research study is to find out the efficacy and safety of whether adding treatment with rindopepimut (also known as CDX-110) to the commonly used chemotherapy drug called temozolomide helps to shrink brain tumors or prevents brain tumors from growing and helps subjects with brain tumors live longer than treatment with temozolomide alone. Temozolomide is a standard treatment for glioblastoma and all subjects in this study will be administered temozolomide according to routine practice. The study will also see how treatment affects your quality of life. Additional studies may be performed to see how your body’s immune system (the system your body uses to fight cancer, infections and “foreign bodies”) is reacting to the treatment. The study will also see what side effects there are when injections of rindopepimut are given along with the commonly used temozolomide chemotherapy.
All patients will receive RT and temozolomide plus concomitant TSC and results will be compared to a historical control (Stupp, 2005) for patients receiving the standard of care (RT and temozolomide), and will include survival data for over 400 patients from the Radiation Therapy Oncology Group (RTOG) 0525 study who received SOC treatment of RT and temozolomide, if results are available. Patients will be assigned to treatment arm sequentially in chronological order of enrollment in the protocol. TSC dose escalation will occur by increasing the number of doses by dosing cohorts. An independent SMC will review each cohort prior to enrollment in the next cohort. The first cohort of 3 patients in the Phase 1 safety lead-in portion will begin at a TSC dosing level of 0.25 mg/kg with a total of 9 TSC doses (3 doses per week over initial 3 weeks of 15 RT sessions). After SMC review with an acceptable safety profile, the number of TSC doses in Cohort 2 will be increased from 9 to 18 doses of TSC with recommended TSC dose from Cohort 1 administered during the 6 weeks of RT and temozolomide. DLT will be determined based on observations through Week 10 of the study, including safety assessments at 4 weeks after completion of all RT sessions. The Phase 2 portion of the study will enroll up to 50 patients at the recommended dose from the safety lead-in study after SMC safety review. TSC will be dosed 3 times a week at 45 to 75 minutes prior to the RT sessions. A total of 9 or 18 doses of TSC, depending on cohort assignment, will be administered during the initial 3 or 6 weeks of RT sessions (Monday, Wednesday and Friday dosing preferred).
Children with progressive and recurrent pediatric brain tumors:
Standard of care therapy for many progressive and recurrent pediatric brain tumors is a combination of radiation to the affected area of brain and temozolomide during and after radiation therapy. However, in spite of being standard of care, these therapies have dismal overall survival rates. Valproic acid is an agent that increases the death of brain tumor cells when given with temozolomide. Therefore, the combination of these two agents in treatment of pediatric brain tumors is promising. Since valproic acid is not approved for this use in the treatment of pediatric patients, it is considered an “experimental” drug.
The study is designed as a randomized, placebo-controlled, double blinded, multi-center Phase II clinical trial. The trial will enroll approximately 240 patients with newly diagnosed GBM into the investigational arm, of which approximately 160 patients will be randomized into the treatment cohort and will receive DCVax-Brain as adjuvant therapy to standard treatment and approximately 80 patients will be randomized into the placebo cohort and will receive standard treatment
supplemented with autologous PBMC (placebo). An additional, separate informational arm will be composed of patients who display progressive GBM at completion of radiation/chemo-therapy, or who are otherwise determined to be ineligible for the investigational arm of the study after leukapheresis.
Patients in the treatment cohort will receive up to 10 immunizations with DCVax-Brain over a period of 3 years. Patients in the placebo cohort will receive up to 10 immunizations with autologous PBMC over a period of 3 years. Patients in the informational arm will receive up to 10 immunizations with DCVax-Brain over a period of 3 years.
This study is for patients 21 years and younger with a brain tumor that has not responded to treatment or has come back after treatment. The purpose of this study is to find out how safe and effective treatment with high dose temozolomide, thiotepa and carboplatin with stem cell rescue followed by 13-cisretinoic acid has on children and adolescents with recurrent/refractory brain tumors. Before study treatment, patients will receive chemotherapy to decrease the size of the tumor. During this chemotherapy, patients will have their stem cells collected. After collection, the stem cells are frozen and stored until they are needed after the high dose chemotherapy (temozolmide, thiotepa and carboplatin). Patients will receive the 13-cis-retinoic acid 6 to 10 weeks after stem cell rescue. It is given for 14 days followed by a 14 day rest period. This cycle is given 6 times for a total of 6 months of treatment. Patients will be treated on this study for about 7 to 8 months.
This study is for patients with a low grade glioma (a slow growing tumor in the brain). The purpose of this study is to compare the effects, good and/or bad, of adding the chemotherapy pill temozolomide to radiation. Temozolomide is an experimental drug for low-grade gliomas. Patients will be randomly assigned to 1 of 2 groups. One group will receive radiation alone, while the other group receives Temozolomide chemotherapy in addition to the radiation. Patients will receive radiation for 5.5 weeks; patients may also take temozolomide during the 5.5 weeks of radiation and for up to one year thereafter. Follow-up exams will occur every 3 months for 15 years.