View clinical trials related to Metastatic Melanoma.
Filter by:Assess the safety and tumor response of utilizing an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine given in combination with standard of care (SoC) checkpoint inhibitors (CPI) in patients with stage IV melanoma with measurable disease.
The goal of the Phase 1 study was to find the recommended Phase 2 dose of the study drug IMO-2125 (tilsotolimod) that can be given in combination with ipilimumab (ipi) or pembrolizumab (pembro) to participants with metastatic melanoma and assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity when administered in combination with ipilimumab or pembrolizumab.
To evaluate the best sequencing approach with the combination of target agents (LGX818 plus MEK162) and the combination of immunomodulatory antibodies (ipilimumab plus nivolumab) in patients with metastatic melanoma and BRAF V600 mutation.
This randomized phase II trial studies how well giving pembrolizumab with standard chemotherapy, tumor infiltrating lymphocytes (TIL), and aldesleukin works in treating patients with melanoma that has spread to other areas of the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving an infusion of TIL, or white blood cells, may help stimulate the immune system to help kill more cells. Aldesleukin may also stimulate the white blood cells to kill melanoma cells. Giving pembrolizumab together with standard chemotherapy, TIL, and high- or low-dose aldesleukin may help stop the melanoma from spreading.
This study evaluates the safety as well as the potential clinical efficacy of an adoptive transfer of CD8+ T cells, sorted with HLA-peptide multimers and specific for Melan-A and MELOE-1 melanoma antigens, to patients suffering from advanced metastatic melanoma (stages IIIc and IV).
The purpose of this study is to investigate the side effects and safety, and effectiveness of combining dabrafenib and trametinib with radiotherapy. Previous and ongoing clinical trials have demonstrated the effectiveness and safety of combining both dabrafenib and trametinib compared with dabrafenib alone. This has led to the approval for the use of both drugs in combination in people with metastatic melanoma with the BRAF mutation. Melanoma that has spread to other parts of the body may also benefit from radiotherapy to help reduce symptoms from melanoma. Previous studies have shown that melanoma may be sensitive to radiotherapy and that it can help to improve quality of life. The intention of the CombiRT study is to establish if dabrafenib, trametinib and radiotherapy combined is a safe and effective treatment for metastatic melanoma.
Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 are administered to support T cell activation and proliferation in vivo. In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy.
Background: Adoptive T cell therapy with tumor infiltrating lymphocytes (TILs) has been reported to induce durable clinical responses in patients with metastatic melanoma. From patients own tumor material T cells are extracted, expanded and activated in vitro in a 4-6 weeks culture period. Before TIL infusion patients are preconditioned with a lymphodepleting chemotherapeutic regimen. After TIL infusion, patients are treated with IL-2 to support T cell activation and expansion in vivo. The BRAF inhibitor is an approved treatment of metastatic melanoma and functions by selectively inhibiting the BRAF mutated enzyme, consequently halting the proliferation of tumor cells. Furthermore, in vitro tests have shown that vemurafenib has immunomodulatory effects that are hypothesized to synergize with TIL therapy, which has been confirmed in animal studies. Objectives: - To evaluate safety and feasibility when combining vemurafenib and ACT with TILs. - To evaluate treatment related immune responses - To evaluate clinical efficacy Design: - Patients will be screened with a physical exam, medical history, blood samples and ECG. - Patients will start vemurafenib 960 mg BID and will continue during TIL preparation. - 7 days after start of vemurafenib, patients will undergo surgery to harvest tumor material for TIL production. - Patient stops vemurafenib and is admitted day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. - On day 0 patients receive TIL infusion and shortly after starts IL-2 infusion continually following the decrescendo regimen. - The patients will followed until progression or up to 5 years.
Recent progresses have been made in the treatment of metastatic melanoma, nevertheless improved patient survival is still limited because of primary resistance and relapses. It is therefore important to continue to understand the molecular mechanisms involved in melanoma development and progression to improve the management of patients. Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. It is now known that senescent cells secrete some factors that exert a pro-tumoral role but the potential existence and the role of insoluble factors remain undetermined. Preliminary results from the investigators laboratory indicate the presence in the senescent secretome of exosomes; microvesicles involved in intercellular communication, immunomodulatory functions, and tumorigenesis. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells. Their interest in oncology as a prognostic factor and marker of therapeutic response is increasing. Thus, our project aims to study the effect of exosomes produced by senescent melanoma cells in the development and progression of melanoma in vitro and in vivo using cell cultures and animal models. In addition, the investigator propose a pilot study whose objective is to determine the effect of vemurafenib on nanovesicles produced by patients with advanced unresectable or metastatic melanoma. The investigator hope to show that exosomes participate in the process of drug resistance and relapse, with the goal of developing (with the exosomes study) theranostic tools for personalized care in patients.
This study is being done to see if using the study drug, pembrolizumab, can shrink down melanoma tumors enough so that they will be small enough to cut out, so that there will be no cancer left in the body. Eligible participants include those who have not received any systemic melanoma therapies (i.e. participants do not have to fail ipilimumab or BRAF inhibitor) and those who have failed all available systemic options (if the participant meets other inclusion / exclusion criteria).