Active clinical trials for "Colorectal Neoplasms"

The incidence of colorectal cancer ranks the third in the world and the mortality ranks the second in the world. The incidence and mortality of colorectal cancer have increased in China in the past decade. The incidence of colorectal cancer is associated with dietary patterns, obesity and lifestyle. The 2010 colorectal cancer survey in China showed that the incidence of colorectal cancer was low in the age group below 50 years old, and began to increase rapidly in the age group above 50 years old, reached the maximum in the age group above 70 years old, and decreased after 80 years old. For advanced colorectal cancer, systemic chemotherapy, local radiotherapy, synchronous or sequential chemoradiotherapy are lack of specificity, killing tumor cells as well as human normal cells, and the space for the traditional cytotoxic chemotherapy drugs to further improve the clinical efficacy of anti-malignant tumor is very limited. Therefore, molecular targeted tumor therapy with strong specificity and relatively small toxic and side effects has gradually become the fourth treatment mode following the three conventional treatment methods of surgery, radiotherapy and chemotherapy. Epidermal growth factor receptor (EGFR) is a clear target for treatment of advanced colorectal cancer. Immunotherapy has been a hot topic in recent years, In the field of colorectal cancer, studies on MSI-H population have been carried out successively since ASCO in 2015.However, the MSI-H population accounts for only 5% of patients with advanced colorectal cancer and 12-15% of total colorectal cancer, and the benefit population is very limited. Cetuximab is approved for the treatment of advanced colorectal cancer in the United States, Europe and China. Cetuximab in combination with chemotherapy is the standard treatment for RAS wild-type (RAS-WT) colorectal cancer. PD-1 monotherapy has been approved for patients with MSI-H/ DMMR colorectal cancer. The approved PD-1 mAb includes Nivolumab and Pembrolizumab. In some small trials, PD-1 monoclonal antibody combined with Regorafenib showed initial efficacy in patients with MSS type advanced colorectal cancer. EGFR signaling pathway blocker combined with PD-1 antibody, a new treatment mode, is of great significance to enrich the content of immunotherapy for patients with colorectal cancer, improve the survival prognosis of patients, and search for new efficacy predictors. In conclusion, this study, on the one hand, is expected to confirm that RAS and RAF wild-type advanced colorectal cancer and MSS type can benefit from Sintilimab combined with Regorafenib treatment, and at the same time, observe the effective rate of this regimen in the mutant group, so as to provide reference for clinical selection.

This phase II trial studies the effect of avapritinib in treating malignant solid tumors that have a genetic change (mutation) in CKIT or PDGFRA and have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Avapritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Avapritinib may help to control the growth of malignant solid tumors.

Colorectal cancer remains the commonest cancer among men, and third commonest among women in Saudi Arabia . Presentation with metastatic disease occurs in almost one third of patients , with 5-year survival decreasing significantly from 90% in stage 1 to 14% once the disease is metastatic . There is enthusiasm in the potential for liquid biopsies to provide easily accessible genetic biomarkers for mutational cancer characterization . Epidermal growth factor receptor (EGFR) monoclonal antibodies are widely used in the treatment of advanced colorectal cancer that do not harbor RAS mutations (RAS wild type). Hence genotyping of oncogenic RAS mutations is essential prior to the initiation of systemic therapy for such patients as the presence of these mutations predict resistance to EGFR targeted antibodies such as Cetuximab and Panitumumab . Detection of such mutations has been done on tissue biopsies with the disadvantage of this being an invasive procedure, and data suggesting that such testing may not be reflective of the true mutational burden of the disease since a single fragment of tissue may be inadequate to reflect the intratumoral heterogeneity. There is increasing evidence suggesting that liquid biopsies or blood based mutational profiling can provide a more comprehensive molecular profile of the disease, and carries the advantage of being minimally invasive. Serial liquid biopsies can act as a tool to identify spatial and temporal heterogeneity predicting response or resistance to targeted agents, and can shed light into the emergence (or disappearance) of specific mutations that may potentially be targeted with newer anti cancer agents . Circulating cell free DNA (cfDNA) consists of small nucleic acid fragments liberated from cells by rupture, necrosis or apoptosis, and is now increasingly being used to detect RAS (and other) mutations in patients with advanced colorectal cancers. KRAS has remained an "undruggable" target for decades until the most recent evidence that showed a new anticancer drug that targets KRAS G12C mutation. The investigators aim to perform cfDNA testing on patients with advanced colorectal cancers who have no RAS mutations (and hence start on EGFR inhibitors) as baseline, compare the results with mutational analysis on fresh tumor tissue, and perform cfDNA at first progression to determine what mutations have emerged, and specifically look for KRAS G12C mutation, which can be targeted with a new novel anti cancer drug . These patients will be collected over a 12 month period (with the aim of performing this on at least 100 patients), and followed from diagnosis (with baseline cfDNA) and until progression on EGFR inhibitors (where another cfDNA sample will be taken). A detailed proposal delineating this process will follow once accepted. This project is unique as it examines mechanisms of resistance to anti-EGFR inhibitors in our patients with advanced colorectal cancers, determines the prevalence of a specific mutation using liquid biopsies and examining cfDNA use, and may have therapeutic implications in facilitating obtaining KRAS G12C inhibitors for such patients.

To investigate whether perioperative electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function after colorectal cancer operation

The purpose of the study is to investigate the safety, tolerability, and preliminary anti-neoplastic activity of S095029 alone and in combination with Sym021 in patients with advanced solid tumor malignancies followed by an expansion phase of triple combinations.

Colorectal cancer (CRC) is the 2nd to 3rd most common malignant disease in developed countries, with over 1 million new cases and 500,000 deaths worldwide each year. The primary treatment for early stage CRC is surgery to remove the tumour, which is possible in 80% of patients. Even after surgery up to half of patients will develop recurrence or spread of the disease (metastases) which is incurable. Survival after 5 years is approximately 14% for patients with metastatic disease. Clinical trials using immunotherapy drugs called 'immune checkpoint inhibitors' have shown excellent results in advanced colorectal cancer patients who have certain genetic characteristics called 'mismatch repair deficiency (MMR-d)' and 'high microsatellite instability (MSI-h)'. The benefits of immunotherapy as a treatment prior to surgery to remove the tumour (neoadjuvant treatment) has been observed in both melanoma and in glioblastoma with enhanced local and systemic anti-tumour responses. Pembrolizumab is an immunotherapy drug and works by helping the body's own immune system to fight the cancer cells. The NEOPRISM-CRC trial will investigate whether giving pembrolizumab before surgery is safe, and whether it improves the chances of the tumour being removed completely, and whether this delays or prevents the cancer from coming back. Pembrolizumab treatment lasts for a maximum of 9 weeks (maximum of 3 cycles of treatment, each cycle consisting of 3 weeks) and is given prior to surgery. Following surgery patients will be followed up for at least 3 years after their surgery and to a maximum of 5 years. Target recruitment is 32 patients and recruitment is expected to take place over a 24 month period. Blood, tissue, mouth swabs and stool samples will be collected from patients throughout the trial to better understand the biology of immunotherapy as a treatment for CRC prior to surgery.

This study is to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of JAB-21822 in combination with cetuximab in patients with advanced colorectal cancer，advanced small intestine cancer and advanced appendiceal cancer with KRAS p.G12C mutation.

Recurrence of liver metastasis in colorectal cancer after R0 resection is mainly due to the invisible minimal residual disease, which are the main factors leading to metastasis and recurrence. Positive circulating tumor DNA (ctDNA) is the direct evidence of the minimal residual disease (MRD). In recent years, Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) has made great breakthroughs, and has achieved good therapeutic effects in hematological tumors, but the research on solid tumors is limited. CEA expression is generally elevated in gastrointestinal tumors and is associated with high aggressiveness of tumors. At present, solid tumor cell therapy targeting CEA has been carried out at home and abroad, and has achieved certain efficacy. Anti-CEA CAR-T cells targeting CEA have been constructed in the pre-clinical study of this project, and the pre-clinical study results suggest good safety and effectiveness. Formation of minimal residual disease is associated with circulating blood in the residual tumor cells. Using this feature, this project intends to conduct a phase I clinical study on patients with minimal residual disease /positive ctDNA after R0 resection of colorectal cancer liver metastasis, so as to conduct preliminary exploration of anti-CEA CAR-T cell therapy, evaluate the safety and effectiveness of the therapy, determine the maximum tolerated dose (MTD), and provide guidance for subsequent drug dosage and clinical trials.

Umbrella study structure to independently and simultaneously assess the effects of the association of durvalumab and tazemetostat in multiple solid tumors.

To determine the efficacy and safety of surufatinib, toripalimab and chemotherapy in second-line RAS/BRAF mutant and MSS colorectal cancer