Active clinical trials for "Neoplasms"

Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in recurrent glioblastoma multiforme.

This early phase I pilot trial studies how well vemurafenib, cobimetinib, and atezolizumab work in treating patients with high-risk stage III melanoma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving vemurafenib, cobimetinib, and atezolizumab may work better in treating high-risk stage III melanoma. Giving atezolizumab and tiragolumab together may also work better in treating high-risk stage III melanoma.

A multicenter, prospective, single arm, non randomized clinical trial to evaluate the safety and efficacy of the C2 CryoBalloon Focal Ablation System (CbFAS) for the treatment of persistent dysplasia or intestinal metaplasia (IM) in the tubular esophagus after 3 or more radiofrequency ablations (RFA) for dysplastic BE, or <50% eradication of Barrett's Esophagus (BE) after 2 RFA treatments.

Up to 50% of soft tissue sarcoma (STS) patients will develop metastases in the course of their disease. Cytotoxic therapy is a standard treatment in this setting but yields average tumor response rates of 25% at first line and ≤10% at later lines. It is also limited in the number of lines and courses by tolerance issues. Trials include poly/oligometastases indistinctively and suggest that consolidation ablation is used in ~20% of patients with residual oligometastases refractory to chemotherapy. Oligometastases represent a stage of disease between completely absent and widely metastatic, and which might be cured if the limited numbers of metastatic sites are eradicated. Ablative strategies to treat patients with oligometastases from sarcomas yield prolonged survival times and stereotactic body radiation therapy (SBRT) is associated with excellent tolerance. Surgery may be offered in selected metastatic cases. Alternatively and increasingly, SBRT yields high control rates at treated sites (≥ 80%). The so-called radioresistance of sarcomas is overcome by the high doses per fraction made possible owing to the high precision achieved with SBRT. SBRT is an accepted treatment strategy provided that tumor burden remains limited in the number and size of metastases. Systemic treatment can be combined with SBRT. SBRT may produce abscopal effects where tumors outside the irradiation area also demonstrate tumor shrinkage in some occurrences. SBRT produces systemic antitumoral immune response in certain conditions and enhances radiation-induced tumor cell death compared to conventional lower dose irradiation. Abscopal effects have been potentialized with SBRT/immunotherapy in several tumor models. Sarcomas are a privileged target tumor given their high metastatic propensity. Several potent immunomodulators that skew the tumor immune microenvironment toward a proimmunity context are being investigated in STS either alone or in combination with chemotherapy or targeted therapy. The PD-1 receptor is present within the tumor microenvironment, and limits the activity of infiltrating cytotoxic T lymphocytes, thus blocking effective immune responses. The action of PD-1 is triggered upon binding to its ligands. PD-1 can stimulate the immunosuppressive function of regulatory T cells. Moreover, blockade of PD-1 can stimulate anti-tumor immune responses. Significant responses have been obtained in several sarcomas with acceptable tolerance. Preliminary clinical experience suggests that immunotherapy can be efficient in refractory leiomyosarcomas. Several drugs targeting the PD-1/PD-L1/2 axis are ongoing either as single agents or in combination with ipilimumab, kinase inhibitors, or chemotherapy in STS subtypes. Combination of radiotherapy with immunotherapy is included as a means of increasing tumor antigen release in metastatic STS. Immunomodulated SBRT is a particularly attractive strategy, given the potential of radiation to induce cytotoxicity in tumors and induce abscopal effects. A phase II radiation trial showed increased apoptosis-, intra-tumoral dendritic cells and accumulation of intratumoral T cells in STS with correlation with tumor-specific immune responses. We here propose a randomized phase II study to prolong progression-free survival (PFS) with the combination of SBRT/immunotherapy in oligometastatic STS patients. SBRT is well-tolerated with hardly any severe toxicity (fewer than 5% acute and late grade 3 toxicities). It is performed in an ambulatory setting in only a few treatment fractions. Associations between irradiation and immunomodulatory agents appear to be synergistic and show favorable tolerance profiles. Immunomodulatory agents have a more favorable toxicity profile than cytotoxic agents with about 65% overall acute toxicities. Immunotherapy selectively binds to PD-L1 and competitively blocks its interaction with PD-1. Compared with anti-PD-1 antibodies that target T-cells, immunotherapy targets tumor cells, and is therefore may induce fewer side effects, including a lower risk of autoimmune-related safety issues, as blockade of PD-L1 leaves the PD-L2 - PD-1 pathway intact to promote peripheral self-tolerance. Stereotactic irradiation is associated with an excellent tolerance with rates of grade 3 or more toxicities below 5%. Preliminary data of toxicity with the association of stereotactic irradiation and immunotherapy show no cumulative toxicity in association with immunotherapy. However, their incidence and characteristics are no different from that observed with stereotactic irradiation alone. Moreover, intracranial metastases are exceptional in sarcomas. The toxicity of the association for extracranial stereotactic irradiation does not seem to be increased either.

Phase II clinical trial, monocentric, not controlled, in patients with high grade cervical intraepithelial lesions. A total of 62 patients with a diagnosis of CIN II, III or carcinoma in situ will be included. It is expected that with the combination of natural products Glizigen® and Ocoxin®-Viusid® at least 60% of patients with treated intraepithelial lesions (IEL) have a global response (complete or partial), with elimination of the human papillomavirus and the viral load.

This phase II trial studies the use of human papillomavirus (HPV) deoxyribonucleic acid (DNA) plasmids therapeutic vaccine VGX-3100 (VGX-3100) and electroporation in treating patients with human immunodeficiency virus (HIV)-positive high-grade anal lesions. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells. Electroporation helps pores in your body's cells take in the drug to strengthen your immune system's response. Giving VGX-3100 and electroporation together may work better in treating patients with high-grade anal lesions.

Previous reports suggest benefit of neoadjuvant chemotherapy/chemoradiation treatment for borderline resectable cholangiocarcinoma. This study is a single center prospective phase II study of neoadjuvant chemotherapy with mFOLFOXIRI in patients with borderline resectable cholangiocarcinoma.

The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in combination with Vorinostat in patients with Recurrent or Progressive neuroblastoma

Study design: Randomised, controlled, multi-centre, open-label, phase III trial (with a single intervention registration phase). Primary Objectives The primary objectives of this study are to determine: The impact on Depth of Response (DoR: less than VGPR versus VGPR or better) when salvage ASCT conditioning is augmented by the addition of a proteasome inhibitor The influence of a consolidation and maintenance strategy on the Durability of Response (DuR:PFS) Secondary objectives The secondary objectives of this study are to determine: Overall survival Time to disease progression The overall response rate following ixazomib, thalidomide and dexamethasone (ITD) re-induction Time to next treatment Progression-free survival 2 (PFS2) Duration of response Minimal Residual Disease (MRD) negative rate post re-induction, post-ASCT and conversion after ITD consolidation Engraftment kinetics Toxicity and safety Quality of life (QoL) Participant population (refer to protocol section 9 for a full list of eligibility criteria). Relapsed MM (with measurable disease by IMWG criteria) previously treated with ASCT First progressive disease (PD) at least 12 months since first ASCT, requiring therapy. ECOG Performance Status 0-2 Aged at least 18 years Adequate full blood count and renal, hepatobiliary, pulmonary and cardiac function Written informed consent Interventions: All participants will be registered at trial entry and will receive re-induction therapy with 4-6, 28-day cycles of ixazomib, thalidomide and dexamethasone (ITD), in order to reach maximum response. Participants who achieve at least stable disease (SD) will be randomised on a 1:1 basis to receive either conventional ASCT (ASCTCon), using melphalan, or augmented ASCT (ASCTAug), using melphalan with ixazomib. All participants achieving or maintaining a minimal response (MR) or better following trial ASCT will undergo a second randomisation to consolidation and maintenance or no further treatment. Participants randomised to consolidation and maintenance will receive treatment as follows: consolidation with 2 cycles of ITD and maintenance with ixazomib until disease progression. Number of participants: 406 participants will be registered into the trial to allow 284 participants to be randomised at the first randomisation (R1) and 248 participants to be randomised at the second randomisation (R2).

This phase II trial studies how well cemiplimab works before surgery in treating patients with stage II-IV head and neck cutaneous squamous cell cancer that has come back (recurrent) and can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.