Active clinical trials for "Colorectal Neoplasms"

This is a follow-on study to the VELOUR trial (NCT00561470). The aim of this study is to acquire the archived colorectal cancer and metastasized tissue tumour blocks of patients who have participated in the VELOUR study. These samples will be analysed to find proteins or markers which represent how an individual may be responding to treatment. The identification of these markers may help provide personalised and more effective treatment programs for patients with similar conditions in the future.

Colorectal cancers are the leading cancers for both sexes combined. They represent 15-20% of all cancers. This cancer has a severe prognosis, the survival rate at 5 years is around 55% and in France it is estimated, all colorectal cancers are responsible for an annual mortality of 15,000 patients. The prognosis of colon cancer knows no significant improvement. The treatment of colon cancer is surgical. It is intended for removal of colonic segment bearing the tumor with margins of healthy colon. The therapeutic attitude following the surgery is essentially driven by histopathology of the tumor. Adjuvant chemotherapy for all patients with localized stage II provides no benefit because the effectiveness of chemotherapy is limited and vulnerable to systemic toxicity. However, nearly 30% of patients with stage II disease will have a recurrence / metastasis. These patients could benefit from adjuvant chemotherapy. Intense research efforts have been made to identify markers predictive of relapse. Over thirty biological markers (eg. Mutations, deletions, chromosomal instability, ...) were highlighted. None of them has so far sufficient prognostic value (independent of TNM) to justify routine application in clinical practice in order to adapt the treatment of patients. The identification of new prognostic markers is a major issue for colorectal cancer. We showed that the intratumoral density memory T lymphocytes (CD45RO) and cytotoxic (CD8) strongly influenced the clinical outcome of patients. We have developed and validated a "immunoscore" technique intratumoral immune quantification and creates a platform to facilitate the clinical immuno transfer. We are currently conducting a large international retrospective study (22 centers,> 9000 patients) with promotion of cancer immunotherapy Company (SITC) to validate the method "immunoscore." At the same time, we are conducting a prospective multicenter study "ImmuCol" (National PHRC) to validate the prognostic value of "immunoscore" in colorectal cancer stage I-IV. The goal of inclusion has been achieved, as 420 patients were included for 18 months. Clinical follow-up will be 3 years after surgery. The program ImmuCol2 research takes advantage of the ImmuCol study to extend the investigation beyond the immunoscore to define the combination of interest, prognostic and theranostic parameters at diagnosis and during the clinical course patients with an objective of personalized medicine.

Adenocarcinoma of the colon and rectum is a common, serious disease and it is the second cause of death from cancer in Spain. The prognosis of CRC depends to a great extent on its stage when diagnosed. Patients with advanced disease, who present up to 40% of all patients, have a poor prognosis. Although the application of modern chemotherapy and radiotherapy treatments obtains median survival periods of around 24 months, the proportion of patients with advanced disease who obtain a cure is low. Systemic treatment of advanced CRC has changed considerably in the last ten years with the introduction of active drugs such as oxaliplatin, irinotecan, and capecitabine. The most commonly used first line regimens are 5-Fluorouracil-Leucovorin-Oxaliplatin (FOLFOX), Capecitabine-Oxaliplatin (XELOX), 5-Fluorouracil-Leucovorin-Irinotecan (FOLFIRI) and, to a lesser extent, Capecitabine-Irinotecan (XELIRI). Chemotherapy regimens are combined with different agents against therapeutic targets, three of which are effective in colon cancer: bevacizumab, which targets vascular endothelial growth factor (VEGF) and cetuximab or panitumumab, which target the epidermal growth factor receptor (EGFR). The use of cetuximab and panitumumab is not recommended in patients with KRAS mutations and the combination of a VEGF and EGFR agents is not beneficial. Two recent studies results have identified KRAS mutations as frequent drivers of acquired resistance to cetuximab and panitumumab in colorectal cancer patients. The conclusions indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression by a DNA Blood Test (Inostics´BEAMing Technology). Centro Integral Oncológico Clara Campal (CIOCC) is aiming to undertake a pioneer project aimed at integrating the analysis of KRAS switch status by BEAMing Technology in patients with metastatic colorectal cancer, tumor KRAS wild-type and BEAMing wild-type treated with first line FOLFIRI-cetuximab In naive chemotherapy tumor-KRAS wild-type metastatic colorectal cancer patients, who are BEAMing positive (KRAS mutated in blood) before treatment may have worse evolution in terms of PFS (progression Free Survival) and response rate than BEAMing negative (KRAS native in blood) patients. To know the proportion of patients who are BEAMing positive (KRAS mutation can be detected in circulating extracellular DNA) at the beginning of treatment, could be of great importance for treatment efficacy.

Colectomy is the most commonly used therapeutic approach for the treatment of non-metastatic colorectal cancer. This approach is generally very effective however the rate of recurrence and the appearance of metachronous metastasis remains a major problem in the postoperative period. One of the hypothesis that can explain this tumor progression is the dissemination of tumor cells at the time of tumor mobilization. In this work, we wish to verify this hypothesis by comparing two surgical technics used in our department for left or right colectomies: respectively either first section of the mesenteric vessels followed by the mobilization of the tumor or first mobilization of the tumor followed by the section of the mesenteric vessels. To evaluate the dissemination, we will study two disseminations markers that have shown their prognostic value: i) circulating tumor cells (which represent a direct marker of dissemination) and ii) tumor circulating DNA (which is an indirect marker) but has the advantage of being more representative of all tumor clones and therefore the tumor burden released into the blood at the time of surgery).

Up to 25% of newly diagnosed patients with colorectal cancer (CRC) have liver metastases (LM). Simultaneous colorectal and hepatic resection has been proven to be a safe and effective approach in dealing with metastatic colorectal cancer. The aim of this paper is to analyse perioperative and oncological outcomes of minimally invasive (laparoscopic and robotic) one-stage simultaneous resection of liver metastases and colorectal tumor in selected patients affected by colorectal cancer and synchronous liver metastases.

Evaluation of individual peripheral blood circulating tumor cells combined with tumor marker detection of efficacy of chemotherapy in patients with advanced colorectal cancer: A observational clinical trial

The CLiFF Study will assess changes in liver function and liver fat in patients with colorectal liver metastases (CLM) undergoing pre-operative chemotherapy before liver resection. There will be no change to the standard treatment for CLM. The change in liver fat will be assessed using novel magnetic resonance techniques and the change in liver function will be measured using a newly-developed fully-licensed breath test to give the most accurate measure of liver function possible. Understanding if these changes are related or reversible will help to understand the relationship between obesity and cancer. This is an important issue, as obesity is now the second most common cause of cancer worldwide.

To evaluate the emergence of RAS mutation in patients with metastatic colorectal cancer, circulating free DNA will be analyzed using mass spectrometric genotyping in subjects during cetuximab treatment. The hypothesis of this study is that acquired RAS mutation is responsible for the resistance to cetuximab treatment in wild-type colorectal cancer. The usefulness of liquid biopsy to monitor dynamic genetic alterations in colorectal cancer during treatment will also be investigated in this study.

Colorectal cancer (CRC), second leading cause of cancer worldwide, is associated with a poor prognosis, especially in patients with advanced disease. Therefore, there is still a need to develop new prognostic tools to replace or supplement those routinely used, with the aim to optimize treatment strategies. Studies on gut microbiota composition provide new strategies to identify powerful biomarkers. Indeed, beyond its beneficial functions for the host, increasing evidences suggest that gut microbiota is a key factor involved in CRC carcinogenesis. Many clinical studies have described an imbalance in the gut microbiota (dysbiosis) in CRC patients, with the emergence of pathogenic bacterial species, Recent studies reported that pks-positive E. coli, a pathogenic bacterial producing toxin encoded by the pks genomic island, is more frequently detected in CRC patients, suggesting a possible role in tumor development. Therefore, this suggests the potential use of microbial signatures associated with CRC for prognostic assessment. Furthermore, influence of body composition profile (BMI, sarcopenia, metabolic syndrome) also appears to be a new relevant prognostic tool regarding surgical and oncological outcomes following CRC surgery. The aim of this translational research project is to study the impact of these new prognostic tools on surgical and oncologic results in a prospective cohort of patients who underwent CRC surgery at the Digestive Surgery Department of the University Hospital of Clermont-Ferrand (France). This could allow to optimize treatment strategies and provide new ways to identify news promising biomarkers associations in order to better define high risk patients. Investigators aim to identify specific microbial signatures associated with some metabolic profiles in order to improve surgical morbidity and/or response to cancer therapies.

By monitoring the serum ctDNA mutational profile using NGS, the present clinical trial aims to elucidate the correlation between the postoperative ctDNA status and the prognosis of patients with early and intermediate-stage colorectal cancer, and explore the possibility of clinical utility of serum ctDNA as a clinical index to predict postoperative relapse.