Active clinical trials for "Adenomatous Polyposis Coli"

Duodenal carcinomas are the leading cause of mortality in patients with Familial Adenomatous Polyposis (FAP) who underwent prophylactic colorectal surgery. The purpose of this study is to determine wether celecoxib combined with ursodeoxycholic acid is an effective chemoprevention strategy to influence the progression of duodenal adenomas to carcinomas in patients with FAP.

The principle objective of this study is to validate confocal endomicroscopy (CEM) in a national, multicenter study, in terms of its ability to diagnose neoplastic lesions in vivo, in two groups of patients at high risk of colorectal cancer (CRC): patients with familial adenomatous polyposis (FAP) after colectomy in whom the neoplastic lesions are probably under-diagnosed, and patients with inflammatory bowel diseases (IBD) in whom endoscopic surveillance is particularly difficult. Methods: The study will be comprised of two phases (Phase I and II). Phase I will serve to validate at the multicenter level the results of the first, recently published, monocenter German study in terms of capacity of CEM to identify the colonic neoplastic lesions in vivo. Phase II is destined to prospectively evaluate the diagnostic yield of CEM in detection and prediction of neoplastic lesions by developing and adding new features to the confocal pattern of in vivo diagnosis. Two cohorts of patients will be studied in parallel: Patients with inflammatory bowel diseases (IBD), like ulcerative colitis (UC) or Crohn's disease (CD), including those before planned colectomy, and patients with FAP after colectomy. During lower endoscopy performed under general anaesthesia, each colonic segment will be examined before and after staining with indigo-carmin. After intra-venous fluorescein injection, all macroscopically abnormal lesions will be examined by CEM, then biopsied. In parallel, multiple random biopsies will be performed, each coupled with simultaneous CEM "optical biopsy" at the same point. In addition, during Phase II, in IBD patients before planned colectomy and in patients with FAP, a "mapping" of colonic mucosa, by obtaining a very high number of CEM "optical biopsies", will be performed, and will be correlated with standard histology performed either on colectomy specimens (IBD) or on standard biopsies (FAP). Principal analysis (Phase I and II) will include evaluation of inter-observer variation in terms of interpretation of in vivo histology and diagnostic yield of CEM with respect to the detection of neoplastic lesions by evaluation of sensitivity and specificity, using standard histology as reference method. Additional analysis (Phase II) will be performed to evaluate the diagnostic and predictive (CRC risk) value of "colonic mapping" by correlating optical images pattern score to results of standard histology. Expected results: This study should guarantee high quality data, standardization of procedures and of interpretation of CEM images, which are prerequisite for dissemination of CEM in clinical practice. The investigators expect to show that CME allows to reliably discriminate between neoplastic and non-neoplastic lesions, that, compared to standard histology, provides better characterization of lesions, especially in the context of extended lesions like in IBD, an finally, that CME images can be used to develop a new "optical biopsy"-based score allowing prediction of high CRC risk in patients with FAP and IBD. The investigators believe that CEM may increase, as compared to currently used techniques, the diagnostic yield in terms of probability of the detection of neoplastic lesions in patients at high risk of CCR, and may become a new standard for endoscopic surveillance in these patients.

This will be a prospective, multi-center, randomized, single blind study to collect and evaluate post-market clinical data on the SprayShield Adhesion Barrier System as an adjuvant to good surgical technique for the reduction of postoperative adhesion formation following major open abdominal surgery.

This pilot clinical trial studies fluorine (F)-18 16 alpha-fluoroestradiol (18F-FES) positron emission tomography (PET)/computed tomography (CT) in imaging patients with desmoid tumors. 18F-FES binds to estrogen receptors, which are present on desmoid tumors, and gives off radiation that may be detected by PET and CT scans. The PET/CT scan forms an image that may show where tumor cells with estrogen receptors can be found in the body.

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.

A Phase 2, randomized, double blind, placebo controlled trial for the effectivness of wholistic turmeric supplementation on polyp burden mong patients with Familial Adenomatouse Polyposis (FAP). Fourty Patients will be randomly assigned in a 1:1 ratio to recieve treatment with 8 capsuls (2*4 capsuls/day) of wholistic Turmeric capsules (Pukka herbs) or placebo for six months.

Familial adenomatous polyposis (FAP) leads to adenomas and eventual adenocarcinomas in colon and less frequently, duodenum. Chemopreventive strategies have been studied in FAP patients to delay the development of adenomas and cancers. The non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitor have shown the regression of colorectal and duodenal adenomas in FAP patients. However, these drugs showed gastrointestinal damage and cardiovascular risks, and new preventive strategies are needed. Niclosamide, an anti-helminthic drug, has recently been suggested to have a suppressive effect on tumorigenesis via inhibition of Wnt pathway, and have no significant safety issues. The investigators devised a double-blind randomized controlled trial to evaluate the effect of niclosamide on polyps of colorectum and duodenum in FAP patients.

RATIONALE: Exisulind may be effective in preventing the development and growth of polyps in patients who have familial adenomatous polyposis. PURPOSE: Randomized phase II/III trial to determine the effectiveness of exisulind in preventing the development and growth of polyps in patients who have familial adenomatous polyposis.

Hypothesis:The Adnab-9 antigen is a predictive biomarker in individuals at risk of developing colorectal neoplasia. Study aim is to evaluate the potential of the Adnab-9 monoclonal antibody (MAb) as a marker of cancer risk in a population at increased risk for colorectal cancer (CRC). This marker would be compared to other current and emerging diagnostic methods. 2,800 Veterans would be recruited into the study. In phase 1, candidates would be defined as having increased CRC risk by a short questionnaire. Stool samples would be obtained and a semi-quantitative Adnab-9 antigen assay (ELISA) would be determined. Patients with differing high and low estimations of fecal Adnab-9 would undergo colonoscopy at which time other samples of effluent and colonic mucosa would be taken, and a detailed lifestyle and nutritional questionnaire would be completed. The characteristics of the Adnab-9 fecal test as a diagnostic test would be critically determined using the outcome of the colonoscopic and other test results. The patients will be contacted through the mail and by word of mouth. Informed consent will be obtained before the samples are obtained. The participants are clinically defined as high-risk and therefore screening colonoscopy would be likely performed in any event. A number of assays for Adnab-9 are feasible including slot-blot, Western blot, and ELISA. Other stool studies include conventional fecal occult blood tests (FOBT or FIT) that will be performed in tandem. The investigators therefore began this method of collection and obtained consent from over 2000 patients with a similar overall compliance rate with FOBT screening procedures to that reported previously of approximately 50%. Currently the study is no longer enrolling patients at the Detroit VA and is now finalizing data entry. Another 450 patients to be recruited at the Philadelphia VAMC.

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-Azithromycin 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 the investigators will select FAP patients which carry APC nonsense mutations, treat them with Azithromycin 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 non-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 Azithromycin to read-through APC nonsense mutation in FAP patients. The read-through effect of Azithromycin 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 Azithromycin 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 4 month and will be conducted in parallel.