View clinical trials related to Malignant Melanoma.
Filter by:The present monocentric prospective phase 2 study aims to reproduce the results obtained at NIRS thus offering the possibility of obtaining a promising rate of progression-free survival (PFS) and local control (LC) in patients diagnosed with mucosal melanoma of lower genital tract. Systemic treatment with immunotherapy is not the subject of this study but is allowed both in the neoadjuvant and sequential regimens. Melanomas have always been considered poorly radiosensitive. It is now accepted that high LET (Linear Energy Transfer) particle beams, such as carbon ions, can offer a biological advantage, compared to photons treatment, in radio-resistant neoplasms treatment, thanks to their higher biological efficacy (RBE) against tumours with a low α/ ß ratio. In addition, carbon ions have the physical advantage of an inverted depth deposition profile compared to photons, allowing then a steep dose gradients that ensure increased sparing of adjacent healthy organs at risk (OARs).
In this clinical feasibility study the investigators will test and compare two advanced optical imaging technologies, lipid and RNA tape stripping with regards to diagnostic accuracies for fast bedside diagnosis of pigmented skin tumours.
This study will enroll metastatic (Stage IV or inoperable stage III) melanoma (MM) patients carrying a BRAF V600E/K mutation with confirmed primary resistance to standard of care immunotherapy (single agent PD-1 or a combination of CTLA-4/PD-1 blockade). Patients must be naïve to therapy with BRAF+MEK inhibitors, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Study CP-MGC018-02 is a study of vobramitamab duocarmazine (MGC018) in combination with lorigerlimab (MGD019). The study is designed to characterize safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and preliminary antitumor activity. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors including, but not limited to, metastatic castration-resistant prostate cancer (mCRPC), melanoma, pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, and renal cell carcinoma (RCC) will be enrolled. Vobramitamab duocarmazine and lorigerlimab are administered separately on Day 1 of every 4-week (28-day) cycle at the assigned dose for each cohort. Participants who do not meet criteria for study drug discontinuation may receive study drugs for up to 2 years. Tumor assessments are performed every 8 weeks (± 7 days) for the initial 6 months on study drugs, then every 12 weeks (± 21 days) until progressive disease (PD). Participants will be followed for safety throughout the study. .
Dermalyzer is a device intended to be used as a decision support system for assessing cutaneous lesions suspected of being melanomas. The input from the device is not intended to be used as the sole source of information for diagnosis. Intended to be used by medical professionals. The service does not provide any other diagnosis. The study is a pre-marketing, prospective, confirmatory, first in clinical setting, pivotal multi-centre, non-interventional clinical investigation to evaluate the clinical safety, performance and benefit of Dermalyzer in patients with cutaneous lesions where malignant melanoma (MM) cannot be ruled out. Primary objective: The primary objective of the investigation is to determine the diagnostic precision of the device; to answer at which level the AI tool Dermalyzer can identify malignant melanomas among cutaneous lesions that are assessed in clinical use due to any degree of malignancy suspicion. Secondary objectives: A) To evaluate usability and applicability in clinical praxis of Dermalyzer by users (medical professionals), B)To gain an increased knowledge and understanding of how digital tools enhanced co-artificial intelligence can assist physicians with the right support for an earlier diagnosis of malignant melanoma. Exploratory objective: To explore health economic aspects of improved diagnosis support Methods: The subjects will be included from around 30 primary care centers in Sweden. If the subject's lesion(s) is suspected of melanoma or melanoma cannot be ruled out, the subject is asked to participate in the investigation. The investigator examines the subject's lesion(s) and makes the clinical assessment of the subject lesion(s) based on established clinical decision algorithms The investigator takes dermoscopy images according to standard of care and archives the image(s) according to clinical routine. The investigator decides on action, based on his or her MM suspicion (excision at the primary care center or referral for excision or referral to a dermatologist for further assessment). The investigator takes images of the lesion(s) again, this time with a mobile phone, containing the AI software, connected to a dermatoscope, and follows the on-screen instructions. The image is processed by the AI and the results are visible on the screen within seconds. The investigator records how he considers that the degree of suspicion of MM (higher vs lower) would have been affected by the AI SW result if it had been the governing body for the treatment. At study follow-up, the final tumor diagnosis from the histopathology results (melanoma/non melanoma) or by dermatologist assessment (if stated as undoubtedly benign), the degree of agreement between the true final diagmosis and the outcome of the AI decision support is determined, and the diagnostic accuracy in distinguishing melanoma from non-melanoma, in terms of sensitivity and specificity as well the positive and predictive value. The corresponding comparison is performed from the examining investigators estimated clinical degree of suspicion. The clinical investigation will collect information from the users, how participating users (investigators at the site) experience the usability of the AI decision support and attaching applications, from short surveys including the validated System Usability Scale.
The therapy of solid tumors has been revolutionized by immune therapy, in particular, approaches that activate immune T cells in a polyclonal manner through blockade of checkpoint pathways such as PD-1 by administration of monoclonal antibodies. In this study, the investigators will evaluate the adoptive transfer of RAPA-201 cells, which are checkpoint-deficient polyclonal T cells that represent an analogous yet distinct immune therapy treatment platform for solid tumors. RAPA-201 is a second-generation immunotherapy product consisting of reprogrammed autologous CD4+ and CD8+ T cells of Th1/Tc1 cytokine phenotype. First-generation RAPA-101, which was bred for resistance to the mTOR inhibitor rapamycin, demonstrated clear anti-tumor effects in multiple myeloma patients without any product-related adverse events. Second-generation RAPA-201, which have acquired resistance to the mTOR inhibitor temsirolimus, are manufactured ex vivo from peripheral blood mononuclear cells collected from solid tumor patients using a steady-state apheresis. RAPA-201 is also being evaluated for the therapy of relapsed, refractory multiple myeloma and was granted Fast Track Status by the FDA for this indication. The novel RAPA-201 manufacturing platform, which incorporates both an mTOR inhibitor (temsirolimus) and an anti-cancer Th1/Tc1 polarizing agent (IFN-alpha) generates polyclonal T cells with five key characteristics: 1. Th1/Tc1: polarization to anti-cancer Th1 and Tc1 subsets, with commensurate down-regulation of immune suppressive Th2 and regulatory T (TREG) subsets; 2. T Central Memory: expression of a T central memory (TCM) phenotype, which promotes T cell engraftment and persistence for prolonged anti-tumor effects; 3. Temsirolimus-Resistance: acquisition of temsirolimus-resistance, which translates into a multi-faceted anti-apoptotic phenotype that improves T cell fitness in the stringent conditions of the tumor microenvironment; 4. T Cell Quiescence: reduced T cell activation, as evidence by reduced expression of the IL-2 receptor CD25, which reduces T cell-mediated cytokine toxicities such as cytokine-release syndrome (CRS) that limit other forms of T cell therapy; and 5. Reduced Checkpoints: multiple checkpoint inhibitory receptors are markedly reduced on RAPA-201 cells (including but not limited to PD-1, CTLA4, TIM-3, LAG3, and LAIR1), which increases T cell immunity in the checkpoint-replete, immune suppressive tumor microenvironment. This is a Simon 2-stage, non-randomized, open label, multi-site, phase I/II trial of RAPA-201 T immune cell therapy in patients with advanced metastatic, recurrent, and unresectable solid tumors that have recurred or relapsed after prior immune therapy. Patients must have tumor relapse after at least one prior line of therapy and must have refractory status to the most recent regimen, which must include an anti-PD-(L)1 monoclonal antibody. Furthermore, accrual is limited to solid tumor disease types potentially amenable to standard-of-care salvage chemotherapy consisting of the carboplatin + paclitaxel (CP) regimen that will be utilized for host conditioning prior to RAPA-201 therapy. Importantly, carboplatin and paclitaxel are "immunogenic" chemotherapy agents whereby the resultant cancer cell death mechanism is favorable for generation of anti-tumor immune T cell responses. Thus, the CP regimen that this protocol incorporates is intended to directly control tumor progression and indirectly promote anti-tumor T cell immunity. The CP regimen is considered standard-of-care therapy for the following tumor types, which will be focused upon on this RAPA-201 protocol: small cell and non-small cell lung cancer; breast cancer (triple-negative sub-type or relapse after ovarian ablation/suppression); gastric cancer (esophageal and esophageal-gastric-junction adenocarcinoma; gastric adenocarcinoma; esophageal squamous cell carcinoma); head and neck cancer (squamous cell carcinoma of oral cavity, larynx, nasopharynx, and other sites); carcinoma of unknown primary; bladder cancer; and malignant melanoma. Protocol therapy consists of six cycles of standard-of-care chemotherapy (carboplatin + paclitaxel (CP) regimen) administered every 28 days (chemotherapy administered on cycles day 1, 8, and 15). RAPA-201 cells will be administered at a target flat dose of 400 X 10^6 cells per infusion on day 3 of cycles 2 through 6. A sample size of up to 22 patients was selected to determine whether RAPA-201 therapy, when used in combination with the CP regimen, represents an active regimen in solid tumors that are resistant to anti-PD(L)-1 checkpoint inhibitor therapy, as defined by a response rate (≥ PR) consistent with a rate of 35%. The first stage of protocol accrual will consist of n=10 patients; to advance to the second protocol accrual stage, RAPA-201 therapy must result in a tumor response (≥ PR) in at least 2 out of the 10 initial patients.
Patients with Small Cell Lung Cancer, Sarcoma and Malignant Melanoma will be treated with GD2-SADA:177Lu-DOTA complex(The IMP is a two-step radioimmunotherapy, delivered as two separate products GD2-SADA and 177Lu-DOTA) to assess safety and tolerability
This is a first-in-human, phase 1a/1b, multicenter, open-label, dose escalation study of STK-012 as monotherapy and in combination with pembrolizumab in patients with selected advanced solid tumors.
Activation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes by DEC-C during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells. This may increase the overall effectiveness and success of Nivolumab treatment. This pilot clinical trial will demonstrate whether combinatorial immunotherapeutic approaches that target epigenetic immune repression and RIG-I activity can favorably alter the tumor immune cell microenvironment and benefit patients with mucosal melanoma.
The microbiome has the potential to serve as a robust biomarker of clinical response to immunotherapy. Additionally, microbial manipulation, through diet, exercise, prebiotics, probiotics, or microbially-derived metabolites, may prove to be beneficial in promoting anti-tumor immune responses. However, large prospective studies in humans with longitudinal sample collection and standardized methods are needed to understand how microbiota and their byproducts affect cancer therapies, particularly among patients undergoing identical therapy but experiencing different outcomes. The proposed observational study builds upon these hypotheses by proposing a large cohort design to further assess the associations between the gut microbiota (composition and function), host immune system, and ICI treatment efficacy across multiple cancer types.