Neoplasms

Digestive System Diseases

All Conditions

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Herbal and Botanical

Mechlorethamine

Lysine

Glutamine

Cola

topical spray; fluorescently-labeled peptide composed of a 7-amino acid sequence \[Gln-Arg-His-Lys-Pro-Arg-Glu\] attached via a 5 amino acid linker \[Gly-Gly-Gly-Ser-Lys\] to a near-infrared fluorophore, Cy5. The complete peptide sequence is written as: Gln-Arg-His-Lys-Pro-Arg-Glu-Gly-Gly-Gly-Ser-Lys(Cy5)-NH2, and is abbreviated as: QRHKPRE-GGGSK-(Cy5)-NH2.

QRH-882260 Heptapeptide

Endoscope used for providing the light via laser to image the area of interest in the colon after the QRH has been sprayed and rinsed.

Scanning Fiber Endoscope

D K Turgeon, MD

A Phase 1B study of the efficacy of a topically-administered 7-amino acid peptide labeled with a near-infrared fluorophore Cy5 for detecting neoplastic areas of the colon is proposed. The study will test the efficacy of administering this agent (QRH-882260 Heptapeptide) to human subjects undergoing clinically-indicated colonoscopy for endoscopic resection of known colonic adenomas or for surveillance biopsies of known dysplasia in the setting of irritable bowel disease (IBD). Up to 120 evaluable subjects will be enrolled.

Subjects will be recruited around scheduled standard of care procedures. The endoscopists performing the procedures are all endoscopists credentialed at the University of Michigan to do these procedures. Urine for dipstick pregnancy testing (if applicable) will be collected before the procedure, along with medical information. Vital signs are routinely monitored throughout the clinical procedure and are available in the electronic medical record. The endoscopy will proceed per the University of Michigan Health System (UMHS) standard of care. The endoscopist performing the clinical procedure will evaluate the potential risk (if any) for the subject to continue with the procedure or study. Five mL of the reconstituted QRH-882260 Heptapeptide (\~100 μM) will be sprayed onto the site of interest through a catheter in the endoscope. Five minutes after QRH-882260 Heptapeptide application, the unbound peptide will be washed off using the endogator irrigator and the residual liquid will be suctioned. Pictures with white-light and fluorescence will be taken with the scanning fiber based molecular imaging endoscopic probe inserted via the instrument channel of the standard endoscope before the QRH-882260 Heptapeptide application, immediately after application and then again after the QRH-882260 Heptapeptide will be washed off. The area of interest identified will be resected/biopsied per discretion of the endoscopist per clinical care. All specimens taken are for clinical care only (not research use) and will be sent for routine histology per UMHS standard of care.

Study of QRH-882260 Heptapeptide Application in the Colon

Phase IB Study of QRH-882260 Heptapeptide Application in the Colon

The test product efficacy will be assessed by evaluating the fluorescence intensified measured from suspicious regions of colonic mucosa where the fluorescently-labeled peptide (QRH-882260) is administered. Measurement of peptide binding will be evaluated by the fluorescence intensity measured from the suspicious (target) region and normal tissues (background) to produce a target-to-background ratio.

Continued monitoring of safety in subjects as measured by the number of Adverse Event (AE) assessments, severity (grade), and relationship to the study drug (any that could be related).

Danielle Kim Turgeon

Professor of Internal Medicine

Adenoma

Adenoma, Villous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroprotective Agents

Flavonoid

Other Dietary Supplements

Epigallocatechin gallate

Epigallocatechin

Catechin

Epicatechin

Powdered decaffeinated green tea extract of Camellia Sinensis, packed in hard gelatine capsules containing either 150 mg EGCG, bid for 3 years

Placebo, packed in hard gelatine capsules, bid for 3 years

Powdered decaffeinated green tea extract of Camellia Sinensis, packed in hard gelatine capsules containing either 150 mg EGCG

* Run-in period with 150mg EGCG two times daily (p.o) for 4 weeks
* 150mg EGCG two times daily (p.o.) over the course of three years.
* Colonoscopy after 3 years

Green tea extract of Camellia Sinensis

Powdered decaffeinated green tea extract of Camellia Sinensis, packed in hard gelatine capsules containing either 150 mg EGCG

* Run-in period with 150mg EGCG two times daily (p.o.) for 4 weeks
* Placebo two times daily (p.o.) over the course of three years
* Colonoscopy after 3 years

Green tea extract of Camellia Sinensis followed by placebo

Julia Stingl, Prof.Dr.med

Thomas Seufferlein, Prof.Dr.med.

This is a randomized, placebo controlled, multicentric trial to investigate the effect of diet supplementation with green tea extract containing 300mg epigallocatechin gallate (EGCG), the major polyphenol of green tea, on the recurrence of colon adenomas.

Prevention of colorectal cancer is a major health care issue because of the high incidence of this cancer. So far, pharmaceutical chemoprevention has not gained widespread acceptance due to side effects of the chemopreventive agents used. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and clinical trials. However, controlled trials demonstrating the efficacy of nutraceuticals fo the prevention of colorectal cancer are largely missing.

The investigators present this randomized, placebo controlled, multicentric trial to investigate the effect of diet supplementation with green tea extract containing 300mg epigallocatechin gallate (EGCG), the major polyphenol of green tea, on the recurrence of colon adenomas.

Patients who underwent polypectomy for colonic polyps will be randomized after a one month verum run-in period to receive either 150mg EGCG two times daily or placebo over the course of three years. The beneficial safety profile of decaffeinated green tea extract, the quantifiable and known active content EGCG, and the accumulating evidence on its cancer preventive potential require in our view a validation of this compound for the "nutriprevention" of colorectal adenoma. Good accessibility and low costs might render this nutraceutical a top candidate for a wider use as food supplement in colon cancer prevention.

Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract -MIRACLE-

Genetic and biochemical biomarkers for recurrence of adenoma or development of dysplasia and carcinoma (blood samples and histological in tissue samples of the colorectal lesions)

University of Ulm

KKS Netzwerk

Deutsche Krebshilfe e.V., Bonn (Germany)

Martin-Luther-Universität Halle-Wittenberg

Prof. Dr. med.

Symptoms and General Pathology

Polyps

60 minutes/session of aerobic exercise, 6 d/week at 50-50% HHR. All sessions will begin with 10 minutes of stretching and 5 minutes of warm-up, and will end with 5 minutes of cool down.

Exercise

There is strong observational epidemiologic evidence that physical activity is inversely associated with risk of colon cancer occurrence in both men and women. This association has been found in over 30 observational studies, and appears to be independent of effects of diet, body fat mass, and other potential confounding factors. Prior to large-scale recommendations regarding exercise as a means of preventing colon cancer, however, more information is needed regarding the type of exercise, when it must be initiated, and how much must be done, in order to produce a protective effect. Information on the mechanisms and biological pathways through which exercise might protect the colon will aid in developing the answers to these questions.

This is a randomized controlled trial of a one-year moderate/vigorous exercise intervention vs. delayed- exercise control on various biomarkers of colon cancer risk in persons that have undergone a colonoscopy within the past 36 months.. The trial is designed to establish the effects of the exercise intervention on colorectal cell proliferation and terminal differentiation, and on factors that may lie in the pathway between exercise and proliferation and apoptosis, in colon and rectal epithelium. It will provide data on: 1) the efficacy of a one-year moderate intensity aerobic exercise program in modulating these processes to a pattern considered low risk for colon cancer, and 2) the mechanisms whereby exercise may lower colon cancer risk in humans. To the investigators' knowledge, this will be the first study of its kind.

The specific aims of the proposed study are:

1. To measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. a delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on proliferation rate in the upper part of colon and rectal mucosa crypts.
2. To also measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on:

   * expression of apoptosis-related proteins (bax/bcl-2 ratio) in colon and rectal mucosal biopsies
   * rectal mucosal prostaglandin levels
   * fasting serum/plasma insulin, glucose, triglycerides, insulin-like growth factor 1(IGF-1), and IGF binding protein-3 (IGFPB-3)
   * body fat mass and distribution (body mass index, waist and hip circumferences, bioelectrical impedance, DEXA scan)
   * subcutaneous abdominal and intra-abdominal fat mass (measured by one-slice CT scan at the L4 level)
   * fitness (VO2max)
   * quality of life (measured by standardized self-report instruments)
   * sleep quality

Effect of Exercise on Biomarkers of Colon Cancer Risk

Exercise Intervention Trial for Colorectal Polyp Patients

Fred Hutchinson Cancer Center

Anne McTiernan, MD, PhD

Chlorophyllin

Protective Agents

Participants will complete the 4 week intervention, 4 week washout, then 4 week control period (monitor only)

Participants will complete the 4 week control period (monitor only), 4 week washout, then 4 week intervention

Participants will be provided frozen dark leafy green vegetables, and counseled to consume 1 cup cooked dark green leafy vegetables (2 servings) daily over the 4 week period while maintaining their normal red meat intake. This will occur during the first 4 week period of the study.

High chlorophyll diet - intervention 1st

Participants will be provided frozen dark leafy green vegetables, and counseled to consume 1 cup cooked dark green leafy vegetables (2 servings) daily over the 4 week period while maintaining their normal red meat intake. This will occur during the last 4 week period of the study.

High chlorophyll diet - control 1st

Andrew D Fruge, PhD, RD

Colon cancer is the third most common cancer in men and women and over 70% of cases are preventable. A western diet, characterized by low vegetable and high red and processed meat intake, indisputably increases colon cancer risk. Heme, which gives red meat its color, is highly reactive, induces hyperproliferation and promotes DNA damage in the colon to a greater degree than any other red meat-associated carcinogen. Preclinical models indicate dietary chlorophyll, which gives green leafy vegetables their color, binds and stabilizes heme in the lumen, preventing genotoxicity. Additionally, data from our randomized controlled weight loss trial indicate increasing red meat consumption has deleterious effects on the gut microbiome, which is also implicated in colon cancer etiology. Because heme-containing foods are the richest sources of bioavailable iron and several other vitamins and minerals, mitigating their potential risks may be more beneficial than eliminating meat, poultry, fish and seafood in their entirety from the diet for risk reduction.

This feasibility study will begin to explore the research question: Will adding chlorophyll-rich green leafy vegetables to the diet prevent the deleterious effects of heme-rich red meat on the human host and microbiome? The investigators will randomly assign 50 adults at increased risk of colorectal adenoma to a block randomized crossover study with two 4-week dietary regimens in which: 1) participants will be provided with frozen green leafy vegetables and counseled to consume a high chlorophyll diet including 1 cup per day of cooked green leafy vegetables and normal meat (high heme) consumption; or 2) continue their normal high heme, low chlorophyll diet (control). A 4-week washout period encouraging habitual diet will be employed between the intervention periods and data will be collected at all four time points.

This study is critical in translating preclinical findings and has the potential to open the door to new knowledge and standards of care in colon cancer prevention. This study is a required step to aid in the design of a larger RCT to determine whether increased green leafy vegetable consumption mitigates the negative effects of red meat on DNA damage, inflammatory cytokines and gut microbe composition. This could lead to equally beneficial dietary guidance for colon health that might be more easily attained by the general public through addition, rather than omission of specific foods.

Fifty thousand cases of colon and rectal cancer (CRC) could be prevented each year through screening, increased exercise and improved diet. Obesity alone increases risk of CRC by 33% and is associated with increased CRC mortality. Red and processed meat consumption is associated with increased CRC risk, most often in the context of dietary patterns, which juxtapose "Western" and "prudent" diets. A recent meta-analysis of 24 case control studies and 11 prospective cohort studies (n=1,295,063 men and women) found an 18% reduction in risk for colon cancer in the groups consuming the highest levels of cruciferous and green leafy vegetables. Risk reduction with high green leafy vegetable consumption remained significant regardless of whether pooled studies controlled for meat and/or total energy intake.

Heme-induced genotoxicity of the colon is prevented by chlorophyll in rodent models; an important finding that has not been tested in clinical trials though is supported by epidemiological observation.

This trial utilizes a crossover design to assess the feasibility of a dietary intervention in adults at increased risk of CRC. The overall intent of this line of research is to elucidate a CRC risk-reducing dietary pattern that is accessible to the general public. Therefore, obese, meat-eating participants will be randomized to an intervention and control diet: 1) high chlorophyll (green leafy vegetables) and high heme (normal meat) consumption; and 2) habitual high heme, low chlorophyll diet (control). During the intervention periods, all participants will receive individual dietary counseling from a registered dietitian two days per week to reinforce daily consumption goals based on the amounts of chlorophyll and heme in various foods. This study translates preclinical models, utilizes an appropriate at-risk population, and if feasible, has the potential to be tested for efficacy for the reduction of colon cancer risk.

Participants will be recruited through the Auburn University Pharmaceutical Care Clinic and throughout the Auburn community. After completing all baseline procedures, participants will be block randomized by gender due to potential differences in fecal microbiome. All participants will receive the intervention; the order in which it is received will be randomly generated. For the high chlorophyll study arm, a goal of 1 cup cooked dark leafy green vegetables will be prescribed, and participants will be instructed to consume at least ½ cup cooked dark green leafy vegetables during the same meal they consume red meat. The high chlorophyll group will also receive a variety of frozen dark green leafy vegetables, including, spinach, kale, collards, mustard greens, and turnip greens. Frozen vegetables are provided because flash-freezing minimizes nutrient loss and prevents chlorophyll degradation. Though the chlorophyll content varies between these species, it is exponentially higher than other green vegetables in the brassica family. Participants will be instructed to consume cooked vegetables, rather than raw, to increase the bioavailability of chlorophyll and reduce the volume of the needed amount of vegetable.

After each 4-week period, participants will complete questionnaires, return unused frozen vegetables (which will be tracked), provide a stool sample, and undergo phlebotomy. Study staff will obtain two 24-hour dietary recalls on non-consecutive days. Participants will be provided with an additional fecal collection kit for the sample that will be obtained prior to the next dietary arm assignment.

The behavioral framework of this intervention will utilize Social Cognitive Theory as the basis for behavior change in each intervention arm. Participants will increase self-efficacy of dietary adherence by setting goals and logging daily food intake (self-monitoring), which will be assessed in twice weekly counseling sessions with a registered dietitian.

4 week intervention and control periods will be delivered and separated by a 4 week washout. The order of intervention and control periods will be randomly allocated

Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults

Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults: The Meat and Three Greens Feasibility Trial

Retain 90% of sample at crossover and 80% at completion

Meet chlorophyll intake goals 90% of days

16s changes in microbiota alpha diversity

Body fat percentage using Bioelectrical Impedence Analysis

Acceptability of the diets will be measured by the Food Acceptability Questionnaire (FAQ) total score. The FAQ is a 10 item questionnaire scored on a 7-point likert scale with total scores ranging from 7-70.

Auburn University

Assistant Professor and Director, Didactic Program in Dietetics

Colonic Polyps

Adenomatous Polyps

Pathological Conditions, Anatomical

Micronutrients

Bone Density Conservation Agents

Gastrointestinal Agents

Vitamins

Vitamin D

Cholecalciferol

Calcium

Calcium Carbonate

Calcium, Dietary

Ergocalciferols

Trace Elements

Hormones

Vitamin D3

Calciferol

Ergocalciferol

Vitamin D2

Calcium 2,000 mg/day as calcium carbonate in two divided doses with food

Vitamin D3 800 IU given as 400 IU twice daily with food over 6 months

Calcium 2,000 mg (as calcium carbonate) + vitamin D3 800 IU given in equal divided doses twice daily with meals over 6 months

Calcium 2,000 mg (as calcium carbonate) + vitamin D3 800 IU given in equal divided doses twice daily with food over 6 months

Calcium and vitamin D3 combined

Placebo

Calcium 2,000 mg/day as calcium carbonate in two divided doses with meals over 6 months

Roberd M Bostick, MD, MPH

The purpose of this study is to test whether calcium and/or vitamin D supplementation favorably affects a set of biomarkers of risk for colon cancer in persons who are at higher than average risk for colon cancer (ie, have already undergone the removal of adenomatous polyps, which are known to be precursors to developing colon cancer).

There is strong biologic plausibility and animal experimental evidence for protection against colorectal cancer by calcium and vitamin D, calcium significantly reduced adenoma recurrence in a large clinical trial in humans (yet the previously reported observational evidence, although generally supportive, is inconsistent), and the observational literature strongly supports protection from vitamin D. A close physiological relationship between calcium and vitamin D has long been known. Yet, other than a possible reduction of colorectal epithelial cell proliferation by calcium, the effects of calcium and vitamin D, individually or jointly, on the normal human colorectal epithelium remain unknown. There have been no clinical trials involving vitamin D individually or jointly with calcium related to colorectal cancer chemoprevention in humans. There are currently no generally accepted pre-neoplastic biomarkers of risk for colorectal cancer other than the possible exception of proliferation markers that, at best, have limited usefulness as individual markers. Based on recent advances in understanding the molecular basis of colorectal cancer, we developed a panel of newer, plausible, reliable, immunohistochemically detected biomarkers that provides molecular phenotyping of the normal appearing colorectal epithelium: 1) inflammation (COX-2), 2) the expression of genes involved in the normal structure and function of the colorectal epithelium that have been found to be altered early in the two major colorectal carcinogenesis pathways (APC, MSH2, MLH1), and 3) a more complete picture of the cell cycle events in colorectal epithelial crypt cells (short and long-term proliferation: MIB-1 and telomerase; differentiation: p21; apoptosis inhibition and promotion: bcl-2, bax, and bak) that has not yet been tested in a chemoprevention trial.

To address these needs, we will conduct a preliminary, randomized, double-blind, placebo-controlled, 2 x 2 factorial chemoprevention trial (n = 88) of calcium 2,000 mg/day and vitamin D3 800 IU/day, alone and in combination vs placebo over 6 months in patients with recent removal of sporadic adenomatous colorectal polyps, to investigate their effects on the individual components and aggregate profile of our colorectal cancer risk biomarker panel. We will also examine study results stratified by NSAID use and Bsm I vitamin D receptor genotypes. The preliminary estimates of treatment effect sizes and variabilities will be used to refine the biomarker panel and study design and to calculate the needed sample size for a potential full-scale study.

We assert that using biological measurements of risk, as they have for ischemic heart disease, will result in a decline in colorectal cancer incidence and mortality. The proposed project is borne of this vision, and has intertwined missions of exploring the efficacy of two plausible and evidentially well-supported dietary agents, calcium and vitamin D, on the modulation of a plausible panel of molecular phenotypic biomarkers of risk for colorectal neoplasia.

Calcium and Vitamin D vs Markers of Adenomatous Polyps

Calcium, Vitamin D, and Colon Cancer Risk Biomarkers

A panel of putative biomarkers of risk for colorectal neoplasms in biopsies of normal appearing rectal mucosa: COX-2, APC, MSH-2, MLH1, MIB-1, telomerase, p21, bcl-2, bax, bak, β-catenin, E-cadherin, TGFα, TGFβ1, calcium sensing receptor, vitamin D receptor, CYP27B1, CYP24, 8-OH-dG

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of QRH-882260 Heptapeptide Application in the Colon	NCT03148119	Colon Cancer Pr...	QRH-882260 Hept... Scanning Fiber ...	18 Years - 100 Years	University of Michigan
Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract -MIRACLE-	NCT01360320	Colorectal Serr... Colorectal Tubu... Colorectal Vill... Colorectal Tubu...	Green tea extra... Green tea extra...	50 Years - 80 Years	Martin-Luther-Universität Halle-Wittenberg
Effect of Exercise on Biomarkers of Colon Cancer Risk	NCT00668161	Colon Cancer Pr...	Exercise	40 Years - 75 Years	Fred Hutchinson Cancer Center
Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract -MIRACLE-	NCT01360320	Colorectal Serr... Colorectal Tubu... Colorectal Vill... Colorectal Tubu...	Green tea extra... Green tea extra...	50 Years - 80 Years	Martin-Luther-Universität Halle-Wittenberg
Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults	NCT03582306	Colon Cancer Pr...	High chlorophyl... High chlorophyl...	18 Years -	Auburn University
Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults	NCT03582306	Colon Cancer Pr...	High chlorophyl... High chlorophyl...	18 Years -	Auburn University
Calcium and Vitamin D vs Markers of Adenomatous Polyps	NCT00208793	Colorectal Aden...	Calcium and vit... Placebo Calcium Vitamin D3	30 Years - 74 Years	Emory University
Effect of Exercise on Biomarkers of Colon Cancer Risk	NCT00668161	Colon Cancer Pr...	Exercise	40 Years - 75 Years	Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for colon cancer prevention