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Testing Nivolumab With or Without Ipilimumab in Deficient Mismatch Repair System (dMMR) Recurrent Endometrial Carcinoma

PRIMARY OBJECTIVE: I. To assess efficacy in terms of progression-free survival (PFS) for immunotherapy with dual immune checkpoint blockade (nivolumab/ipilimumab) versus (vs.) monotherapy (nivolumab) in patients with recurrent mismatch repair (MMR) deficient endometrial carcinoma with measurable or non-measurable (detectable) disease. SECONDARY OBJECTIVES: I. To evaluate the overall survival (OS) as estimated from time of enrollment to last follow-up or death. II. To evaluate the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in those with measurable disease at start of treatment. III. To evaluate progression-free survival at 6 months. IV. To evaluate the nature, frequency and degree of toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. V. To evaluate PFS and objective response rate in patients with prior anti-PD1/PDL1 therapy and compare efficacy of dual immune checkpoint inhibition vs. anti-PD1 monotherapy. OUTLINE: Patients are randomized into 1 of 2 arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle and ipilimumab IV over 90 minutes on day 1 of every other cycle. Cycles repeat every three weeks. Treatment with nivolumab and ipilimumab repeats for up to 8 cycles in the absence of disease progression, unacceptable toxicity, or complete response (CR). Patients then receive nivolumab alone on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression, unacceptable toxicity, or CR. ARM II: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for up to 8 cycles, then every 4 weeks thereafter in the absence of disease progression, unacceptable toxicity, or CR. MAINTENANCE THERAPY: Patients achieving CR on Arm I or II receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity. Additionally, all patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. All patients also undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Patients are followed every 3 months for 2 years, and then, every 6 months for 3 years.

Progesterone Therapeutic Regimen Plus Statins in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia

After diagnosed of AEH or EEC by hysteroscopy, patients meet the study criteria will be enrolled. The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion tissue was detected by Raman scattering instrument. And Age, height, weight, waistline, blood pressure, basic history of infertility and family cancer will be collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), blood lipids, sex hormone levels, anti-müllerian hormone (AMH) and renal/liver function tests will be performed before treatment to evacuate their basic conditions. Each subject will receive body fat testing by Inbody 770. Patients with endometrial cancer who met the inclusion criteria were randomly divided into the control group and the experimental group in a 1:1 ratio according to the random numbers generated in advance. The administration regimen for the two groups was as follows: 1. Control group: progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa 3.75mg subcutaneous injection monthly); 2. Trial group: progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa3.75mg subcutaneous injection monthly) combined with statins (oral atorvastatin calcium tablet 20mg/ day; or rosuvastatin 5mg/ day; or pivastatin 2mg/ day); The specific selection of progesterone regimen was based on whether the patients had oral progesterone contraindications and if BMI≥28kg/m2 was not suitable for oral progesterone, Mirena +GnRHa regimen was selected. The choice of statin drugs is based on the results of the drug sensitivity test of the patient's tumor tissue, and the most sensitive one of the three drugs is selected. For patients remained SD after 9 months of treatment but refused hysterectomy, a multiple disciplinary discussion would be held for individual case, and alternative treatment would be given. Maintenance treatment will be recommended for patients with CR, and participants will be followed up for at least 1 year.

Concurrent Laparoscopic Hysterectomy and Weight Loss Surgery in Obese Patients With Endometrial Carcinoma or Endometrial Intraepithelial Neoplasia

The most common risk factor for endometrial cancer is obesity. However, because early-stage endometrial cancer has a very high survival rate, patients more often suffer from long-term issues related to their weight, like heart disease, stroke, and diabetes. Weight loss surgery has been shown to help patients lose weight and also decrease their risk for obesity-related diseases. This research study is a Feasibility Study. This is the first-time investigators are studying both 1) the referral process of patients with endometrial cancer to the Center for Metabolic and Bariatric Surgery without delaying curative treatment of endometrial cancer 2) the combined surgery of both hysterectomy and weight loss surgery. The combined surgery of hysterectomy and weight loss surgery has been performed both at this institution and others without increased complications, but it has not been formally studied. Approximately 30 patients are expected to participate in this study at Brigham and Women's Hospital (BWH).

Phase 1 Clinical Trial of Lenvatinib, Pembrolizumab and Hypofractionated Pelvic Radiation Therapy for PMMR Recurrent/Unresectable Endometrial Carcinoma

Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma

Clinicopathological Analysis of Endometrial Carcinoma in the View of Old and New International Federation of Gynecology and Obestetrics (FIGO)

Endometrial cancer is the commonest gynecological cancer mostly affecting women in the post-menopausal age group . The average age of women diagnosed with endometrial cancer is 60. It's uncommon in women under the age of 45. The vast majority of endometrial cancers are carcinomas (usually adenocarcinomas). The five-year survival rate for endometrial adenocarcinoma following appropriate treatment is 80%. More than 70% of women diagnosed have Federation of Gynecology and Obestetrics (FIGO) stage I cancer, which has the best prognosis. Stage III and especially Stage IV cancers has a worse prognosis, but these are relatively rare, occurring in only 13% of cases. The median survival time for stage III-IV endometrial cancer is nine to ten months. The FIGO 2023 staging system provides a refined framework for managing endometrial cancer, benefiting patient care and outcomes as the FIGO 2023 staging system for endometrial cancer offers several advantages over the previous FIGO 2009 system 1. Improved Prognostic Prediction: The 2023 system predicts survival more accurately, validated by five studies and It adds granularity to prognostic assessment, identifying treatment-relevant subgroups of patients. 2. Incorporation of Molecular Measures as The 2023 system integrates molecular parameters, reflecting their impact on prognosis (similar to breast cancer staging) 3. Risk Stratification: It incorporates risk stratification, aiding better prognosis definition and treatment decisions. 4. Enhanced Understanding of Endometrial Carcinomas: The 2023 system clarifies the diverse biological nature of endometrial cancers, allowing for better-adapted treatment.

Pembrolizumab With Ataluren in Patients With Metastatic pMMR and dMMR Colorectal Carcinoma or Metastatic dMMR Endometrial Carcinoma: the ATAPEMBRO Study

In controlling tumor outgrowth an intact immune surveillance is very important. PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress this immune control. Pembrolizumab is a potent and highly selective humanized monoclonal antibody designed to directly block the interaction between PD-1 and its ligands and is registered for the treatment of advanced (unresectable or metastatic) melanoma of locally advanced or metastatic NSCLC in adults. In an earlier study it's effect has been shown in mismatch repair deficient tumors. Ataluren is designed to allow the protein making apparatus (the ribosome) in cells to skip over a premature stop codon (PTC), allowing the cells to translate the sequence downstream of a premature termination codon (PTC) in mRNA transcripts. This may result in the translation of additional out-of-frame code, which is available in abundance in dMMR tumors. We argue that this may result in new target peptides for the immune-system to recognize cancer cells. The investigators hypothesize that the formation of these peptides by Ataluren can enhance the effect of Pembrolizumab anti-PD1 therapy. Therefore the investigators designed a Single Center, open label, Phase I-II trial designed to test the safety and efficacy of the combination of Ataluren and Pembrolizumab for the treatment of metastatic mismatch repair deficient and proficient colorectal adenocarcinoma and metastatic mismatch repair deficient endometrial carcinoma.