Active clinical trials for "Colorectal Neoplasms"

This will be a pilot study involving 5 patients diagnosed with colorectal carcinoma and treated with pre-operative chemotherapy and external beam radiation therapy at the Jewish General Hospital, whom will very soon undergo surgery. Participants will be sensitized by the instillation of a 250 mL enema containing 1.6 mmol of HAL. The enema will be administered with a plastic tube with an inflatable blocking balloon to prevent leakage of the enema. Fluorescence sigmoidoscopy will be performed with white light then blue excitation light after retention of the enema for 60 minutes, followed by a rest time of up to 30 minutes before rectoscopy. Red fluorescence should be induced by illumination with blue light. Pictures with and without fluorescence will be taken. The patients will undergo a colectomy (partial or complete) within the next 2-3 days and the surgical specimens will be collected for further fluorescence microscopy studies and pathological correlation of fluoresce with malignant pathology/histology as the gold standard. The total concentration of porphyrins in the patients' urine and serum will be recorded before sensitization, immediately after sensitization (instillation of the enema), and approximately 24 hours after sensitization. The patients' pre-and-post operative liver function tests will be measured. Adverse events will be reported by direct questioning of all patients with regards to photosensitivity and gastrointestinal symptoms (nausea, vomiting), and by measuring blood pressure and heart rate. Our objectives and endpoints are: 1) to determine if fluorescence with photodynamic diagnostics is selective for colorectal cancer, 2) to determine if photodynamic diagnostics has the potential to improve the detection of malignant cell after neoadjuvant chemotherapy and radiation, and 3) to determine if photodynamic diagnostics can provide an accurate depiction of the extent of disease burden not visible with normal white light sigmoidoscopy to the naked human eye.

The purpose of this interventional study is to assess the progression free survival (one year) of patients with treatment of FOLFIRI and cetuximab, combined with an optional dermal prophylaxis. Further Objectives: Development of acneiforme follicular exanthema >= grade 2 Duration until development of acneiforme follicular exanthema >= grade 2 Development of paronychia Development skin fissure (hand and foot) Objective remission according RECIST 1.1 Rate of secondary resections of liver metastasis with a curative approach Assessment of safety and tolerability Overall survival Progression free survival

Colorectal Surgery Preoperative Exercise Training is a study being run by the colorectal surgery team at the Norfolk and Norwich University Hospital and the University of East Anglia to look at the role of exercise before surgery to improve recovery following an operation. Having an operation to remove part of the bowel puts physical stress on the body. We know that training can help the body cope with physical stress in the same way that an athlete trains before a competition. We hypothesise that the body may recover more quickly if it is trained prior to an operation with regular and simple exercises. Cardiopulmonary exercise testing (CPET) is used to evaluate the function of the lungs, heart and muscles at rest and during exercise. CPET testing is often done as part of standard pre-operative assessment in many hospitals for patients before undergoing major surgery. Some studies have demonstrated that CPET can be used to predict outcomes following surgery (such as time taken till discharge, complication rates). The study consists of two parts: Study 1) CPET variables to predict outcomes in surgery - patients will undergo a CPET test to determine baseline fitness. Blood tests will be taken around the time of surgery to examine whether biochemical markers in the bloodstream (when used in combination with results from the CPET test) can predict outcomes and recovery following colorectal surgery. Patients will then be monitored to assess their speed of recovery and rate of complications following surgery. This will enable us to determine which CPET variables or combination of variables are most useful in the prediction of post-operative complications following colorectal surgery. 2) The second study will consist of an exercise intervention involving several sessions of supervised exercise in a laboratory. Before and at the end the exercise training regime, CPET measurements will be taken to see if fitness has improved with exercise. This part of of the study is to determine if it is feasible to implement a structured, supervised exercise programme for patients awaiting elective colorectal cancer surgery. The results of this study will be used to inform a larger randomised controlled trial to examine the influence of exercise on CPET variables and postoperative outcomes.

In recent years, anti-angiogenic agents have been incorporated into clinical practice for the treatment of metastatic CRC, leading to improvements in progression-free survival and overall survival. Regorafenib is an oral multi-kinase inhibitor that targets angiogenic and oncogenic kinases. Although structurally similar to another multi-kinase inhibitor, sorafenib, it appears to be pharmacologically more potent and possesses broader antiangiogenic properties. Both sorafenib and regorafenib target BRAF wild-type and BRAF V600E mutant but the inhibition of p38 MAP kinase is a peculiar characteristic of regorafenib. A Phase I study of regorafenib as a single agent in patients with heavily pretreated CRC showed promising clinical activity with a disease control rate (PR + SD) of 59% in evaluable patients. In the Phase III trial (CORRECT), which was a randomized double-blind, placebo-controlled study comparing either regorafenib plus best supportive care (BSC) or placebo plus BSC, it was shown that regorafenib significantly increased overall survival (OS), progression-free survival (PFS) and disease control rate (DCR), independently of KRAS status. A major interest, given the data presented in the CORRECT trial, is to determine predictive biomarkers to indicate patients likely to benefit, or to be resistant to this anti-angiogenic compound. This study aims to determine the efficacy of regorafenib as single-agent treatment for the treatment of second-line metastatic colorectal cancer and to identify predictive biomarkers in the actual metastatic tumors to be treated. In the case of metastatic CRC patients, liver lesions are frequently the most common site of metastatic deposit and these lesions can be biopsied to assess putative biomarkers. Patients will be asked to undergo a biopsy of a metastatic lesion prior to treatment, and an optional liver biopsy at the time of relapse. Using several high-throughput discovery platforms, biomarkers will be identified in the metastatic tumor specimens and in blood samples collected throughout the treatment. This will allow us to evaluate putative biomarkers and monitor tumor biomarker dynamics using serial blood collection. The objectives of this trial are to help identify the patient subgroup most likely to be responsive or resistant to regorafenib, so that future treatment with regorafenib can be directed to the more responsive but as yet identified patient population.

A group of colorectal cancer (CRC) patients treated with chemotherapy and Bevacizumab (Bev) maintain the same sensitivity after progression to maintenance treatment because they remain dependent on VEGF angiogenic mediator, while other patients in whom there is an angiogenic switch (AS) become dependent on other angiogenic cytokines and become resistant to Bev chemotherapy combinations .

Colorectal cancer (CRC) is a leading cause for cancer related mortality in the western world with a lifetime risk of 6%. Etiology is complex, while genetic background significantly affects the risk. Around one third of all genetic disorders as well as most cases of Familial Adenomatous Polyposis (FAP) and a large proportion of all sporadic CRC cases occur as a result of premature nonsense mutations (creating a stop codon) in an individual's adenomatous polyposis coli (APC) gene. Nonsense mutations are single-point alterations in the DNA that prematurely halt the protein translation process, producing a shortened, nonfunctional protein. In many of these cases, if the cell can be 'persuaded' to ignore the premature stop codon signal, the resulting protein may be able to ameliorate or stop the disease. Recently, members of the aminoglycoside family of antibiotics have been found to induce ribosomal read-through of nonsense mutations, leading to expression of a full length, functional protein. Investigators have recently shown that members of the aminoglycoside and macrolide antibiotic families can induce read-through of the nonsense mutations in the APC gene and lead to reduced oncogenic phenotypes in CRC cells and in different mice models. The aim of this project is to determine the ability of the macrolide antibiotic-erythromycin to induce read-through of the nonsense mutations in the APC gene and to induce expression of a full length, functional APC protein in patients suffering from FAP and to tests its effect on adenoma number and size and on desmoid tumors in these patients. The future goal is to maximize the effect of stop-codon suppressors on APC while minimizing side effects. In this study investigators will select FAP patients which carry APC nonsense mutations, treat them with erythromycin PO for 4-6 months and examine colonic and duodenal adenomas as well as abdominal desmoid tumors, that will be documented before during and after treatment. In parallel, investigators will test polyp, adenoma and desmoid tissue samples as well as blood samples from these patients for changes in expression levels of the APC protein and related oncogenic markers. Suppression of nonsense mutations within the APC gene should be of benefit for patients suffering from FAP, attenuated FAP or multiple adenomas and for patients with advanced or diffuse CRC. Furthermore, given the rapid progress being made in the identification of different nonsense mutations in human genes that lead to mostly un-curable disease, the identification of clinically approved compounds that suppress nonsense mutations and that can be administered long-term without significant side effects would open new venues in the treatment of genetic human diseases that arise from pre-mature stop codons in important coding sequences. Immediate goal: establish the ability of erythromycin to read-through APC nonsense mutation in FAP patients. The read-through effect of erythromycin will be clinically tested by counting and measuring the number and size of both colonic and duodenal adenomas before and over treatment and by measuring the size of known desmoid tumors. Samples of the adenomas and desmoid tumors will be tested by western blot, immunofluorescence and immunohistochemistry for restoration of APC expression and changes in oncogenic markers. These experiments should be conducted within 6 month. Long term objective: Determine the lowest dose of erythromycin that can inhibit growth of colonic neoplasia and CRC in patients expressing a truncated APC protein due to nonsense mutations. Examine the ability of a panel of additional macrolide antibiotics to induce APC nonsense mutation suppression using in-vitro methods. Investigators will focus on macrolide antibiotics that are currently in clinical use and are administrated for long terms. These objectives should take around 6 month and will be conducted in parallel.

The primary objectives of this randomized clinical trial are to evaluate if perioperative SDD can reduce clinical anastomotic leakage rate and its septic consequences as well as other infectious complications. By reduction of septic complications long-term oncological outcome might simultaneously improve.

There is still no perfect treatment suggestion for patients with asymptomatic colorectal cancer with unresectable metastatic disease. Whether patients can benefit from palliative resection of primary tumor or not is still waiting for answer. The investigators hypothesis that asymptomatic metastatic colorectal cancer patients who respond to chemotherapy will benefit from primary tumor resection.

First line chemotherapy treatment regimens for metastatic colorectal cancer (mCRC) present disease-free survival of more than 10 months, and as much as 12 and 15 months for many patients. It is evident that there are 2 groups of patients with metastatic colorectal cancer(mCRC): those who progress during first line treatment or in the 6 months following the last chemotherapy infusion and those who progress after this first 6-month period. There are currently no studies evaluating the efficacy of second line chemotherapy regimens according to the duration of response to first line treatment. It seems logical that patients with less aggressive tumours will benefit more from treatments targeting specific proteins, such as panitumumab, due to the shorter duration of these tumours cell cycle, which makes them less sensitive to chemotherapy. This study is therefore justified to determine an increase in activity and control of the disease in patients who progressed after 6 months of the last first line chemotherapy infusion for metastatic colorectal cancer(mCRC) in subjects expressing wild-type KRAS.

This is an open-label, non-randomized, prospective, multicentric, Phase IV study evaluating FOLFIRI/ FOLFOX plus cetuximab in the first-line therapy of subjects with KRAS wild-type metastatic CRC.