Active clinical trials for "Glioblastoma"

CAR T cell immunotherapy has achieved great success in CD19+ B-cell malignancies. Whether this new generation of cell-based immunotherapy can be applied to solid tumors remain to be investigated, partly due to hostile immune-suppressive tumor microenvironment which favors tumor growth but not immune system. Signaling pathway of programmed death 1 (PD-1) and its ligand PD-L1 plays an important role in suppressing immune response against tumors. PD-L1 is over-expressed in 88% of glioblastoma. We constructed a chimeric switch receptor (CSR) containing the extracellular domain of PD1 fused to the transmembrane and cytoplasmic domain of the costimulatory molecule CD28. CSR modified T cells are able to recognize PD-L1-expressing tumor cells and transduce signals to activate T cells, which results in tumor killing. A truncated EGFR (tEGFR) which lacks of the ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the CSR vector and is used for in vivo tracking and ablation of CSR T cells when necessary. This pilot study is to determine the safety and efficacy of autologous CSR T cells in patients with recurrent glioblastoma.

This is a surgical biospecimen collection study. The purpose of this study is to understand how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn off the RAF signaling pathway. This is important because these drugs are currently FDA approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.

A Randomized, Double-Blind, Placebo-Controlled, Parallel, Multi-Center Study to Assess the Efficacy of BRCX014 Combined with Standard-Of-Care Treatment in Subjects with Glioblastoma Multiforme, Multiple Myeloma, and GI Malignancies

Treatment of glioblastoma involves an optimal surgery, followed by a combination of radiation and temozolomide chemotherapy. Progression-free survival (PFS) with this treatment is only 6.9 months and relapse is the norm. The rationale behind the fact that limited chemotherapy agents are available in the treatment of malignant gliomas is related to the blood-brain barrier (BBB), which limits drug entry to the brain. Intraarterial (IA) chemotherapy allows to circumvent this. Using IA delivery of carboplatin, the investigators have observed responses in 70% of patients for a median PFS of 5 months. Median survival from study entry was 11 months, whereas the overall survival 23 months. How can we improve on this? By coupling radiation with a chemotherapeutic which is also a potent radiosensitizer such as carboplatin. Study design: In this phase I/II trial, patients will be treated at recurrence; a surgery will be performed for cytoreduction and to obtain tumor sample, followed with a combination of re-irradiation and IA carboplatin chemotherapy. A careful escalation scheme from 1.5Gy/fraction up to 3.5Gy/fraction will allow the investigators to determine the optimal re-irradiation dose (10 fractions of radiation over 2 weeks). Toxicity will be assessed according to the NCIC common toxicity criteria. Combined with radiation, patients will receive 2 treatments of IA carboplatin, 400 mg/m2, 4 hours prior to the first and the sixth radiation fraction. IA treatments will then be continued on a monthly basis, up to a total of 12 months, or until progression. Outcome measurements: Tumor response will be evaluated using the RANO criteria by magnetic resonance imaging monthly. The investigators will also acquire a sequence that enables the measurement of cerebral blood flow, cerebral blood volume and blood vessel permeability that are all relevant to understand the delivery of therapeutics to the CNS. Primary outcome will be OS and PFS. Secondary outcome will be QOL, neurocognition, and carboplatin delivery. In vitro intracellular carboplatin accumulation: Tumor samples from re-operation will be be analyzed for intracellular Pt concentration by ICP-MS. The amount of Pt bound to DNA will be measured. The level of apoptosis will be determined for each of the sample. Putting together these data will allow to correlate clinical and radiological response to QOL, NC (MOCA), and to delivery surrogates for the IA infusion and intracellular penetration of carboplatin.

The Phase II study to determine the safety and efficacy of V-Boost in treating a type of brain cancer called Glioblastoma Multiforme (GBM). V-Boost is an immunotherapy in which the patient's immune system will be modulated to eliminate tumor cells. V-Boost is made as an oral tablet which contains specially formulated hydrolyzed GBM antigens along with alloantigens. Patients are either newly diagnosed or with recurrent form of GBM who may have been subjected to surgery and/or chemo- or radiation therapy that ended up unsuccessful. The goal is to eradicate GBM tumor cells through daily oral administration of one pill of V-Boost immunotherapeutic vaccine, which so far has not shown any adverse reaction.

TTFields has been approved by the FDA for the treatment of patients with glioblastoma multiforme. However, the clinical effect and safety of radiotherapy concurrent of TTFields is not definite. In this study, the investigators conduct a phase II clinical trial to evaluate the efficacy and safety of this strategy.

Currently,6 cycles of Temozolomide adjuvant chemotherapy after concurrent radiotherapy and Temozolomide chemotherapy(STUPP regimen)for newly diagnosed postoperative GBM can increase the 2-year and 5-year overall survival rates of patients to 26.5% and 9.8%, respectively. However, most patients are still unable to avoid tumor recurrence and death.Anlotinib is an efficient multi-target tyrosine kinase inhibitor (TKI) that effectively block the migration and proliferation of endothelial cells and reduce tumor microvascular density by targeting VEGFRs, FGFRs, PDGFRs. It has been proved to be safe and effective in advanced lung cancer(including NSCLC,SCLC)after second-line standard chemotherapy failure,and advanced soft tissue sarcoma after anthracycline-containing chemotherapy failure.Here, we prepared to evaluate whether the combination of dose-dense Temozolomide and Anlotinib can preferably improved survival of the first recurrent or progressive GBM after STUPP regimen.

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be an effective treatment for glioblastoma multiforme and anaplastic astrocytoma. PURPOSE: Phase I trial to study the effectiveness of immunotoxin therapy in treating children who have progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma

This drug is being developed to treat a type of brain cancer, glioma. This study was developed to evaluate the safety, time to disease progression and survival rates after treatment.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have recurrent glioblastoma multiforme.