Active clinical trials for "Sarcoma, Ewing"

This is an international, multi-centre, single arm Bayesian designed phase 2 study to identify and determine the safety and activity of anti-IGF-1/IR inhibition in patients with relapsed and/or refractory ESFT. Approximately 40 patients will be recruited from 5-7 European centres. Each patient will be treated with single agent linsitinib, 600 mg orally once a day for days 1-3, 8-10 and 15-17 on a 21 day cycle until disease progression or undue toxicity.

This pilot phase I/II trial studies the side effects and best dose of plerixafor after radiation therapy and temozolomide and to see how well it works in treating patients with newly diagnosed high grade glioma. Plerixafor may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill tumor cells. Giving plerixafor after radiation therapy and temozolomide may be an effective treatment for high grade glioma.

The purpose of this study is to find the safe dose of nab-paclitaxel in children with solid tumors, and to see if it works to treat these solid tumors in children and young adults (in Phase 1 ≤ 18 years old and in Phase 2 ≤ 24 years old). After the final dose has been chosen, patients will be enrolled according to the specific solid tumor type, (neuroblastoma, rhabdomyosarcoma, or Ewing's sarcoma), to see how nab-paclitaxel works in treating these tumors.

This is a phase I study designed to determine the feasibility of transplantation using a novel transplant approach that employs a two-stage haploidentical cell infusion following myeloablative conditioning. This strategy, which includes selective depletion of naïve T cells, may speed immune reconstitution thereby potentially reducing the limitations of traditional haploidentical hematopoietic stem cell transplantation (HSCT) and increasing its potential therapeutic application. Additionally, the investigators intend to explore overall survival, event-free survival, hematopoietic cell recovery and engraftment as well as infection rates and complications in these patients.

This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or refractory malignant solid tumors.

This study investigates the safety/toxicity and potential anti-tumor activity of sequential administration of nivolumab and escalating doses of the mTOR inhibitor ABI-009 in advanced Ewing's sarcoma, PEComa, epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urethelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, MSI-H/dMMR metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors

Ewing's sarcoma characterized by the t(11; 22) (q24; q12) translocation at several but prioritized breakpoint sites, resulting in the EWS/FLI1 fusion gene is the second most frequently diagnosed primary malignant bone tumor in the US with an annual incidence, from birth to age 20, of 2.9 cases per million population. The survival rate for patients with high-risk recurrent disease (relapse < 2 years) is < 10% at 5 years. Moreover, of patients who progress after second line treatment, eighty percent do not achieve a second complete response and of these patients < 10% survive one year. Refractory patients to both frontline and second line therapy have even worse prognosis. The EWS/FLI1 gene is well known as the driver gene of Ewing's sarcoma. We designed a novel pbi-shRNA™ EWS/FLI1 Type 1 LPX which has demonstrated sufficient specificity, safety and efficacy in animal testing to justify Phase I testing. Clinical safety (no ≥ grade 3 product related toxic effect) and target specific activity has been observed with other bi-shRNA products involving 147 cancer patients (698 separate dose administrations) (BB-Investigational New Drug (IND) 14205; BB-IND 14938). Moreover, safety has been observed with IV delivery of pbi-shRNA™ EWS/FLI1 Type 1 LPX in murine and swine testing via multidose IV administration.

This is a single-arm, open-label study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of talazoparib in patients with advanced tumors with DNA-repair pathway deficiencies. There will be 2 parts to the study: a dose escalation phase in which the maximum tolerated dose will be defined, and a dose expansion phase.

Patients with relapsed solid tumors such as sarcomas and neuroblastoma have a poor survival, generally < 20%. There is an urgent need for new treatments that are safe and effective. HSV1716, an oncolytic virus, is a mutant herpes simplex virus (HSV) type I, deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells - a phenotype exploited to selectively kill tumor cells. In previous clinical studies, HSV1716 has been shown to be safe when injected at doses up to 10^5 plaque forming units (pfu) directly into human high-grade glioma and into normal brain adjacent to tumour, following excision of high-grade glioma. In an extension study, HSV1716 has been shown to be safe when injected at a dose of up to 10^6 pfu directly into brain tumours. Replication of HSV1716 in human glioblastoma in situ has been demonstrated. Following a single administration of HSV1716 by direct injection into active recurrent tumor or brain adjacent to tumor, some patients have lived longer than might have been expected. This study seeks to evaluate the safety of a single injection of HSV1716 in the treatment of extracranial solid tumors in adolescents and young adults. HSV1716 has also proved safe when given by direct intra-tumoural injection in patients with squamous carcinoma of the head and neck, and in patients with malignant melanoma. Replication of HSV mutants in human sarcomas and neuroblastoma in cultured cells and human xenograft models has been demonstrated. This study is designed in two parts. PART 1 of the study specifies a single dose of virus. Participants who experience at least stable disease or relapse following a determination of stable disease, may qualify for subsequent doses in PART 2. PART 2 requires signing of a separate consent. Funding Source - FDA OOPD

Autologous Vigil™ vaccine expresses rhGMCSF and bi-shRNAfurin from the Vigil™ plasmid. The GMCSF protein is a potent stimulator of the immune system, recruiting immune effectors to the site of intradermal injection and promoting antigen presentation. The furin bifunctional shRNA blocks furin protein production at the post transcriptional and translational levels. This decrease in furin in turn decreases the conversion of the proforms TGFβ1 and TGFβ2 proteins. Also, reduced furin protein levels have a negative feedback inhibition on TGFβ1 and TGFβ2 gene expression, decreasing the levels of their mRNAs. The resulting decrease in TGFβ1 and TGFβ2 proteins reduces the local immunosuppression they cause and promotes tumor surface antigen and MHC protein display.