View clinical trials related to Metastatic Melanoma.
Filter by:Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients metastatic cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-vascular endothelial growth factor receptor (VEGFR2) incorporated in the retrovirus. Objectives: - To determine a safe number of these cells to infuse and to see the safety and effectiveness of cell therapy using anti-VEGFR2 gene modified tumor white blood cells to treat recurrent or relapsed cancer. Eligibility: - Individuals greater than or equal to 18 years of age and less than or equal to 70 years of age who have been diagnosed with metastatic cancer that has not responded to or has relapsed after standard treatment. Design: - Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed - Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-VEGFR2 cells. {Leukapheresis is a common procedure which removes only the white blood cells from the patient.} - Treatment: Once their cells have grown the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-VEGFR2 cells and aldesleukin. They will stay in the hospital for about4 weeks for the treatment. - Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.
This is an Open-label, single-arm, phase II study of ipilimumab in patients with spontaneous preexisting immune response to NY-ESO-1. Preclinical data suggest, that CTLA-4 blockade enhances polyfunctional T cell responses in patients with melanoma. Thus patients with immunological response to NY-ESO-1 might benefit from an anti CTLA-4 treatment. Eligible patients will receive 10 mg/kg ipilimumab every 3 weeks during a 10-week induction period, followed by a radiological assessment in week 12. Patients with clinical benefit (partial response, complete response or stable disease according to the immune-related response criteria) will continue with an ipilimumab administration every 3 months starting at week 24 up to week 48 until the end of the study or until disease progression,toxicities requiring discontinuation
Our proposed study is designed to test the safety of a new vaccine against melanoma. The induction of immune activity against cancers such as melanoma is a promising approach to cancer treatment, but to date, only a few clinically significant immune responses have been seen following vaccine therapy. This is an important problem, since there are very limited treatment options for patients with metastatic melanoma (melanoma that has spread to lymph nodes and organs). Studies suggest that monoclonal antibodies (mAbs) that block inhibitory receptors on immune cells can enhance the immune responses against cancer, but the intravenous injection of such mAbs has caused severe side effects in animals and humans. In our laboratory, we have developed a method to deliver mAbs and other proteins that block such inhibitory receptors locally at the site where immune responses against melanoma proteins are stimulated by vaccination, enhancing anti-melanoma immunity while avoiding the side-effects associated with intravenous injection of these immune modulators. This is achieved by loading dendritic cells, a type of immune cell, with RNA that encodes the immune modulator. The RNA-loaded dendritic cells then make the immune modulatory proteins and release them locally. By mixing these dendritic cells with additional dendritic cells loaded with melanoma proteins, the immune modulators are released at the site where anti-melanoma immune cells are stimulated. In this phase I trial, subjects with metastatic melanoma will undergo the process of leukapheresis, in which white blood cells are removed from the body. Monocytes, a type of immune cell, will then be purified from the white blood cells and cultured under conditions that will change them into dendritic cells. Half of these dendritic cells are then loaded with melanoma antigen RNA, which will lead to the production of melanoma antigen proteins within the dendritic cells. The remaining half of the dendritic cells will be either untreated or loaded with RNA encoding immune modulators so that these dendritic cells will release immune modulators at the site of vaccination. These dendritic cells will be mixed with the melanoma antigen-loaded dendritic cells and injected as a vaccine into lymph nodes. Each subject will receive six weekly injections of their own dendritic cells. Safety and toxicity will be closely monitored. In addition, immune responses against melanoma, as well as clinical responses, will be assessed.
The purpose of this study is to evaluate whether therapy with MORAb-028 is safe, effective, and to determine the appropriate dose of MORAb-028 in the treatment of metastatic melanoma.
Human cancers express tumor antigens that can be targeted by cytolytic T lymphocytes (CTL). These antigens consist of a small peptide, derived from endogenous proteins, that is presented at the cancer cell's surface by an HLA class I molecule. Such antigenic peptides, including MAGE-3.A1 and NA17.A2, have been tested in experimental therapeutic vaccines to elicit CTL responses in cancer patients, mainly with metastatic melanoma. Up to now, only rare tumor responses have been observed. Tumor resistance to CTL killing is the most likely explanation for the poor effectiveness of cancer vaccines. This resistance is probably acquired by the tumor during its development and selected by its repetitive challenge with spontaneous anti-tumoral immune responses. The precise molecular mechanisms of tumor resistance remain unknown. The observation that tumor-infiltrating lymphocytes (TIL) purified from melanoma metastases can recognize and kill autologous tumor cells in vitro, whilst they seem unable to control tumor growth in vivo, suggests that this resistance is hosted by the tumor environment, rather than being the result of a generalized immune suppression. The investigators have developed a murine model of cutaneous graft rejection that mimics the situation in melanoma. Female CBA mice do not reject syngeneic male skin grafts, even though they mount a spontaneous CTL response against H-Y, a male specific minor histocompatibility antigen, following grafting. The investigators have tested various experimental procedures aimed at inducing effective graft rejection in these mice. This was obtained with a combination of IFN-α, IL-2, GM-CSF, each administered separately under the skin graft, associated with topical applications of imiquimod. All these agents are available as registered drugs. Based on this murine model of cutaneous allograft rejection, the investigators postulate that local immunomodulation with this combination can trigger an effective tumor rejection process, and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination.
Background: - Aldesleukin (IL-2) is a drug that can help to shrink tumors in some patients with metastatic renal cancer and metastatic melanoma. It is possible that removing certain white blood cells (known as CD4 cells) before IL-2 treatment may improve the treatment effects. - Zanolimumab is an antibody that works by destroying CD4 cells in the blood. Researchers are interested in determining whether zanolimumab can improve the results of IL-2 treatment if it is given before, during, and after IL-2 treatment. In addition, further research with zanolimumab may provide more information on how IL-2 treatment causes tumors to stop growing or shrink. Objectives: - To evaluate the effectiveness of IL-2 treatment in conjunction with zanolimumab in individuals with metastatic cancer. Eligibility: - Individuals at least 18 years of age who have been diagnosed with metastatic melanoma or metastatic kidney cancer. Design: - Eligible participants will be screened with a full physical examination and medical history, imaging studies, and blood samples, including leukapheresis, to remove a sample of white blood cells for testing purposes. Participants may also have a colonoscopy and biopsies if they have received previous treatments that have been known to cause colon damage. - Participants will be treated with zanolimumab and IL-2 treatment for 9 weeks. - Zanolimumab will be given on an outpatient basis during weeks 1 through 4, 6, 8, and 9. In weeks 5 and 7, participants will receive zanolimumab as an inpatient in addition to IL-2 therapy. - Inpatient IL-2 treatment will be given during weeks 5 and 7. Up to 15 doses of IL-2 treatment will be given over a maximum of 5 days, followed by inpatient recovery time. - During week 5, participants will have tumor imaging studies prior to receiving zanolimumab and IL-2 treatment. - About 2 weeks after the treatment period, participants will return to the clinical center for a 2-day evaluation with a physical examination, imaging studies, and blood samples. - Participants whose tumors have responded to treatment will be offered up to two additional courses of treatment, starting 6 to 8 weeks after the last IL-2 dose. Subsequent courses will be given exactly as described above in the initial course of treatment. Participants whose tumors do not respond to treatment will have follow-up evaluations as required by the study researchers.
This randomized phase II trial is studying how well giving ipilimumab with or without sargramostim (GM-CSF) works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery (unresectable). Ipilimumab works by activating the patient's immune system to fight cancer. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of treatment. It is not yet known whether giving ipilimumab together with sargramostim is more effective than ipilimumab alone in treating melanoma.
This Phase Ib/II study is an open label, multicenter study. The study is divided in two parts: Phase I: an open-label, dose escalation study of F16IL2 in combination with paclitaxel for patients with solid tumours, bladder cancer, breast cancer, metastatic melanoma, mesothelioma, NSCLC, prostate cancer and sarcoma amenable to taxane therapy. Phase II: a prospective, single-arm, multicentre study of a fixed dose of F16IL2 in combination with paclitaxel, equivalent to stage 1 of the Simon two-stage phase II design, for patients with metastatic melanoma, breast cancer and NSCLC amenable to taxane therapy.
The goal of this clinical research study is to learn if combining ipilimumab and temozolomide can help to control metastatic melanoma. The safety of this drug combination will be studied. Researchers would also like to study how this therapy affects the levels of certain chemicals in the blood that are related to your immune system.
Background: - Adoptive cell therapy involves taking white blood cells called lymphocytes from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient to allow the cells to attack the tumor. Because this process is lengthy and difficult to perform, researchers have been developing improved means of performing adoptive cell therapy. Researchers are now interested in comparing adoptive cell therapy with the standard treatment for metastatic melanoma (skin cancer). Objectives: - To compare the effectiveness of adoptive cell therapy with standard high-dose aldesleukin as a treatment for metastatic melanoma. Eligibility: - Individuals 18 years of age or older who have been diagnosed with metastatic melanoma and have not previously received aldesleukin therapy or cell therapy for their disease. - Participants must have at least one tumor that can be easily removed as part of the treatment procedure. Design: - Participants will be screened with a full medical history, physical examination, blood and urine tests, and imaging scans to evaluate tumor size and treatment options. - Participants will be separated into two groups, in which one group will have adoptive cell therapy and one will have aldesleukin treatment. - Adoptive Cell Therapy - Participants will have a tumor sample taken in order to collect white blood cells for treatment. Participants whose tumors do not provide sufficient white blood cells may be switched to the aldesleukin-only treatment group. - The white blood cells will be grown in the laboratory for several weeks. - Prior to receiving cell therapy, participants will receive chemotherapy for 7 days to improve the chances of successful treatment. - Participants will have cell therapy followed by high-dose aldesleukin treatment every 8 hours for up to 5 days. This treatment will be followed by 1 to 2 weeks of recovery time as an inpatient at the clinical center. - Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter.. - Standard Aldesleukin Treatment - Participants will have high-dose aldesleukin treatment every 8 hours for up to 5 days (one cycle of treatment), and will have a second cycle of treatment 7 to 10 days after the first cycle. - If tests show that the tumors have grown, participants will be offered the chance to have additional cycles of aldesleukin, or begin a cell therapy treatment. - Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter.