View clinical trials related to Gastric Cancer.
Filter by:This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-2-307-MAB in patients with advanced cancer
This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-2-307-ADC in patients with advanced cancer
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.
This study intends to explore the value of 68Ga-FAPI-04 and 18F-FDG PET/CT in the evaluation of treatment response to neoadjuvant chemotherapy(NAC) for patients with locally advanced gastric cancer(LAGC).
The goal of the CAFÉ Study is to determine the cancer risks associated with germline CTNNA1 loss-of-function variants.
For locally advanced gastric/gastroesophageal junction adenocarcinoma (cT3/4aN+M0 ), neoadjuvant therapy can downstage T and N stage, improve R0 resection rate, reduce recurrence and metastasis rates, and finally improve the long-term survival. A combination of Fruquintinib and SOX for locally advanced gastric/gastroesophageal junction adenocarcinoma could be a novel therapy. This study intends to evaluate the efficacy of Fruquintinib plus SOX as neoadjuvant therapy for locally advanced gastric or gastroesophageal junction adenocarcinoma.
The main objective of Part 1 is to evaluate the safety and tolerability of bemarituzumab plus 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) and nivolumab. The main objective Part 2 is to compare efficacy of bemarituzumab plus chemotherapy (mFOLFOX6 or capecitabine combined with oxaliplatin (CAPOX)) and nivolumab to placebo plus chemotherapy (mFOLFOX6 or CAPOX) and nivolumab as assessed by overall survival.
This is a first-in-human Phase 1a/1b multicenter, open-label oncology study designed to evaluate the safety and anti-cancer activity of NX-1607 in patients with advanced malignancies.
Helicobacter pylori is a pathogenic bacteria transmitted from individual to individual, being scientifically recognized as an agent who causes persistent inflammatory activity on the gastric mucosa. This pathogen represents a Global Health problem, as shown in a systematic review by Hooi et al. Besides regional differences, more that half of the world population is expected to have already been infected by this bacteria. In Portugal, research studies estimate that more than 80% of the adult population has already contacted with H. pylori. H. pylori infection is associated with active chronic gastritis in every colonized patient, what may consequently lead to peptic ulcer disease, atrophic gastritis, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. For that reason, H. pylori infection is considered to be a disease, independently of the presence of gastrointestinal symptoms. Additionally, H. pylori has been classified as a confirmed carcinogen (class I) by the International Agency for Research, being responsible for carcinogenic pathways conducting to both gastric adenocarcinoma and lymphoma. This fact gains a particular relevance taking into account that gastric cancer is one of the most prevalent cancers worldwide. On other hand, more than 75% of the gastric cancers occur following H. pylori infection. Thus, H. pylori eradication constitutes an essential Public Health measurement, being inclusively considered a cost-effective method to decrease the gastric cancer burden, by promoting pre-malignant lesions regression, such as atrophic gastritis, and by delaying the disease progression in case of intestinal metaplasia or dysplasia. Maastricht V consensus is a document updated in 2016, including the major recommendations regarding H. pylori diagnosis, follow-up and treatment. It highlights the emergence of antibiotic resistances and how they must influence clinical practice, namely the choice of antibiotic regimens, as successful eradication has become less frequent with more prevalent antibiotic resistances. This is the case of clarithromycin and metronidazol, both currently recommended as first-line options by the Portuguese Society of Gastroenterology. In fact, a systematic review conducted in 2018, aiming to evaluate antibiotic resistances on the Portuguese population observed that clarithromycin, metronidazole and double resistance occurred in 42%, 25% and 20% of the individuals, respectively. Nowadays, Maastricht V guidelines recommend quadruple regimens containing bismuth, such as Pylera (r), as the first-line option in areas with significant double resistance to metronidazole and clarithromycin. Another option currently being investigated is the double therapy with amoxicillin in high doses and proton pump inhibitor. This has become a particularly attractive alternative due to its efficacy, good tolerability and significantly low resistance (<1%) among the European population. The aim of this clinical trial is to compare both regimens - pylera (r) and high-dose amoxycillin - in H. pylori eradication, regarding their efficacy, tolerability and side effects, in order to asses viable therapeutic options in a population with progressively increasing resistances to alternative regimens currently recommended.
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.