Active clinical trials for "Rectal Neoplasms"

This is a multi-center, non-randomised Phase 1b study to evaluate the safety and tolerability of ATP128 alone or in combination with BI 754091 and of heterologous prime-boost ATP128 + VSV-GP128 in combination with BI 754091. ATP128 is a self-adjuvanted chimeric recombinant protein vaccine being developed in combination with programmed cell death 1 (PD-1) blockade for the treatment of microsatellite stable (MSS) patients not responding to PD-1 blockade. The PD-1 inhibitor being tested with ATP128 is the BI 754091 (Ezabenlimab) compound which belongs to the human immunoglobulin G4 (IgG4) subclass of antibodies. VSV-GP is a recombinant chimeric vesicular stomatitis virus (VSV, Indiana strain Rhabdoviridae) which carries the envelope glycoprotein (GP) of the visceral non neurotropic WE-HPI strain of the Lymphocytic choriomeningitis virus (LCMV, Arenaviridae) instead of the native VSV glycoprotein (G) and is developed as integral part of the prime-boost regimen together with ATP128. The Sponsor plans to enrol 96 patients with histologically or cytologically confirmed stage IV colorectal cancer coming form three different patient populations: Cohort 1a: 6 patients with stage IV colorectal cancer (CRC) having failed standard of care (SoC) therapies Cohorts 1b, 2a, 2c: 30 patients with stage IV microsatellite stable/mismatch repair-proficient (MSS/MMRp) CRC being in stable disease (SD) or partial response (PR) after first line of SoC (4-6 months duration at minimum) Cohorts 2b, 4b: 30 patients with stage IV MSS/MMRp liver-limited disease Patients eligible for this study will be enrolled in one of the 8 cohorts depending on their disease: Patients in Cohort 1a will receive ATP128 as single agent Patients in Cohorts 1b, 2a, 2b, 2c will receive ATP128 in combination with BI 754091 Patients in Cohorts 3, 4a, 4b will receive ATP128 and VSV-GP128 in combination with BI 754091

This is a phase II/III, multi-center, open-label, 3-arm, randomized controlled trial assessing the efficacy and safety of neoadjuvant long-course chemoradiation combined with Tislelizumab (PD-1 inhibitor) and subsequent TME surgery, by comparing assorted endpoints between two experiment groups (Experiment group 1: chemoradiation+concurrent PD-1 inhibitor; Experiment group 2: chemoradiation+sequential PD-1 inhibitor) with a control group (chemoradiation only).

In patients with locally advanced rectal cancer (LARC), preoperative chemo-radiotherapy (CTRT) is considered the standard of care. Preoperative CTRT approach often results in a significant tumor downstaging and local control, with evidence of complete pathological response (pCR) rate of about 15% in high volume institutions. In high-risk LARC a new strategy called total neoadjuvant therapy (TNT) has emerged, in which systemic chemotherapy with fluorouracil and oxaliplatin (RAPIDO trial) or with the triplet FOLFIRINOX (as was used in the PRODIGE 23 study) is incorporated before or after the administration of short-course RT or neoadjuvant CTRT and prior to surgery. However, given the fact that TNT may represent an overtreatment for a subset of patients, additional therapeutic strategies are warranted to improve the outcomes also in patients with lower risk that are not good candidate for a TNT. In the era of personalized medicine, tumor molecular profiling may lead to the identification of therapeutic targets for pharmacological intervention potentially useful to enhance treatment outcomes. O(6)-methylguanine-DNA-methyltransferase (MGMT) repairs DNA damage induced by alkylating agents and MGMT inactivation due to promoter methylation confers enhanced sensitivity to alkylating agents such as temozolomide (TMZ). TMZ has modest activity in patients with MGMT-methylated pretreated metastatic colorectal cancer and responses are restricted to tumors with complete MGMT loss by immunohistochemistry (IHC) and microsatellite stable (MSS) status. Both capecitabine and temozolomide induces deoxythymidine triphosphate thymidine pool depletion might induce deoxyribonucleic acid (DNA)-double strand breaks and eventually apoptosis in rapidly dividing cells. On the basis of such evidences, there is a strong biological and clinical rationale for testing the addition of TMZ to capecitabine-based CTRT in patients with MGMT silenced and MSS technically resectable LARC. The aim of this trial is investigating whether the addition of TMZ to standard concurrent capecitabine-based long-course chemoradiation may increase pCR rate as compared to historical control in patients with locally advanced rectal cancer not candidate to TNT and molecularly selected for the presence of MGMT silencing and microsatellite stable status.

Diverting ileostomy seems to mitigate the consequences of anastomotic leak from low rectal anastomosis. Gastrointestinal continuity is restored after a period of 6-12 weeks but it can be longer if the patient is on adjuvant chemotherapy or due to low priority given to this procedure. This exposes up to one-third of the patients to significant morbidity having an impact on the quality of life and considerable economic costs. Although no meta-analysis data determined the safety and optimal time for the closure of a temporary diversion of the small bowel, earlier reversal of ileostomies a few days after primary anastomosis reduces the length of exposure to stoma-related morbidity and may improve quality of life, reduce stoma-related costs and still protect the distal anastomosis. Herein, we aimed to assess the results of early closure of defunctioning ileostomy a week following a satisfactory anastomosis, negative air leak test and smooth post-operative course and in absence of worrisome clinical signs of anastomotic leak with optional intraoperative visualization of the anastomostic line by endoscopy immediately before closing the ileostomy.

This phase II trial tests whether adding nivolumab to the usual treatment (encorafenib and cetuximab) works better than the usual treatment alone to shrink tumors in patients with colorectal cancer that has spread to other places in the body (metastatic) or that cannot be removed by surgery (unresectable) and whose tumor has a mutation in a gene called BRAF. Encorafenib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the BRAF gene. It works by blocking the action of mutated BRAF that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab in combination with encorafenib and cetuximab may be more effective than encorafenib and cetuximab alone at stopping tumor growth and spreading in patients with metastatic or unresectable BRAF-mutant colorectal cancer.

This study is a single-center, prospective, open-label, randomized controlled clinical study, and the purpose of this study was to compare the pathological complete response rate (PCR) of patients with locally advanced rectal cancer treated with short-course radiotherapy sequential Tislelizumab combined with CapeOX (group A) versus short-course radiotherapy sequential CapeOX (group B). A total of 100 patients with locally advanced rectal cancer will be enrolled in the study. These patients were randomly assigned to the experimental group (group A) and the control group (group B) in a ratio of 1:1.

The rationale of this clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer using dose-escalated ultra-fractionated short course radiation therapy interdigitated with chemotherapy. We believe delivering short course radiotherapy over a prolonged interval, at escalated doses and with concurrent chemotherapy may be feasible and allow for improved clinical response.

The purpose of this study is to investigate the efficacy and safety of combined fruquintinib、toripalimab and SRT in neoadjuvant therapy for locally advanced rectal cancer.

The goal of this prospective phase II feasibility study is to evaluate two additional local treatment options in rectal cancer patients with a good clinical response after neoadjuvant (chemo)radiation: contact x-ray brachytherapy versus extension of the waiting interval with or without local excision, and to investigate which rate of organ preservation can be achieved.

This study focused on the alterations of gut microbiome and function during defunctioning ileostomy, and observed the effects of probiotic intervention on intestinal microbiome and function. The investigators looked forward to find the specific intestinal maladjusted flora from this work, which could provide a new scheme for the subsequent treatment of the damaged intestinal function and the reduction of the incidence of postoperative complication.