Active clinical trials for "Colorectal Neoplasms"

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.

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.

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.

The aim of the study is to establish the existence of a relationship between the dietary intake of polyunsaturated fatty acids (PUFA) and the risk of colorectal cancer in humans, using 2 reliable and complementary biomarkers: the fatty acid-composition of lipids of the abdominal subcutaneous adipose tissue and the fatty acid composition of erythrocyte phospholipids.

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.

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.

Cancer patients undergo many different modalities of treatments. Pharmacological treatment should be well understood. The nutritional status is not taken into account when calculating drug's doses and this may have an impact in toxicity and quality of life. The present study proposes to evaluate the relationship between the calculation of pharmacological treatment's doses, the toxicity and the impact on quality of life among colorectal and breast cancer's patients.

At present, chemotherapy is widely used in the adjuvant treatment of colorectal cancer patients after surgery. Capecitabine is one of the main chemotherapeutic drugs. But the effect is not good enough, the adverse reaction is serious, and the individual differences were significant. The present study shows that these problems are related to the differences in the exposure of capecitabine and its metabolites in different patients. The genetic biomarkers for capecitabine include DRD, MTHFR and TYMS. Mutations in these genes directly affect the expression of metabolic enzymes involved in capecitabine and control the concentration of capecitabine and its metabolites. However, these markers have been obtained through clinical trials in the United States, and their role in predicting the effectiveness or safety of capecitabine and its metabolites has not been validated in Chinese cancer patients.The study was based on a case study of patients with colorectal cancer in China, and capecitabine as the primary postoperative chemotherapy regimen to verify whether the available biomarkers can be used to predict the effectiveness and safety of capecitabine. To clarify the effect of capecitabine on endogenous metabolites, and to study the mechanism of its effect, so as to discover new biomarkers.

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.

Some data have suggested a clinical survival benefit related to the reintroduction of anti-EGFRs therapy in patients with metastatic colorectal cancer (mCRC). Based on resistance mechanisms related to the development of resistant clones, the investigators could assume that patients who benefited most from the reintroduction of anti-EGFRs were those who, through interval chemotherapy, had no longer mutated RAS clone in plasma that appeared during the progression with the first anti-EGFR treatment. Conversely, those who did not benefit from this therapy were probably patients who had mutated RAS clones circulating at the time of reintroduction of anti-EGFRs. To support this hypothesis, investigators propose to evaluate the correlation between the eventual presence of RAS mutations in circulating blood and the efficacy of an anti-EGFR therapy reintroduction in patients with mCRC.