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Other Dietary Supplements

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Omega 3 Fatty Acid

Cola

Eicosapentanenoic Acid (EPA) as the free fatty acid 2 capsules twice daily for 6 months.

Endoscopy and biopsies taken as described under intervention.

Medium chain triglycerides 2 capsules twice daily for six months. Endoscopy and biopsies taken as described under intervention.

2 x 500mg EPA capsules twice daily for 6 months

Eicosapentanoic Acid (EPA)

Endoscopy with video and photographs at baseline and month 6.

Endoscopy

9 biopsies taken at baseline and month 6 from the rectum of normal mucosa for analysis of apoptosis (3 biopsies), cell proliferation (3 biopsies) and mucosal fatty acid levels (3 biopsies). Two biopsies taken at baseline and month 6 from polyps for cell proliferation (1 biopsy) and apoptosis (1 biopsy).

Biopsies taken

2 x 500mg placebo capsules twice daily for 6 months

Placebo

Nicholas J West, MB BS FRCS

This purpose of this study is to investigate whether the number and size of rectal polyps can be reduced in patients with Familial Adenomatous Polyposis (FAP) by using a highly-purified form of a naturally occurring substance, the omega-3 fatty acid, eicosapentaenoic acid (EPA).

It has been found that people who consume a large amount of oily fish tend to have a lower risk of developing colon cancer. This is thought to be due to the omega-3 fatty acids present in oily fish, one of which is EPA. The effect of taking a 99% pure form of EPA (2g per day) compared with placebo capsules on the number and size of polyps in the rectum over a six month period will be investigated.

FAP is an inherited susceptibility to diffuse colorectal adenomas and colorectal carcinoma, occurring in close to 100% of unresected colons. It is caused by a germline mutation in the Adenomatous Polyposis Coli (APC) gene located in the long arm of chromosome 5. To prevent cancer development it is recommended that patients with FAP undergo colectomy with ileo-anal or ileo-rectal anastomosis (or colectomy and end-ileostomy) at a socially convenient time before polyp progression to malignancy and before the age of 25. Patients with the attenuated FAP phenotype, often associated with mutations at the 5' terminus (exon 4 and proximally), have fewer polyps and may often delay colectomy. Patients with an ileo-rectal anastomosis are still susceptible to polyp formation in the remaining rectal stump and require 6 monthly check-ups with a flexible sigmoidoscope with removal of any polyps that develop. Therefore, an effective chemopreventative agent with a favourable side-effect profile would be of benefit to FAP patients with ileo-rectal anastomosis (IRA) and recurrent rectal polyps in addition to young adults who prefer to delay colectomy. If such an agent were to be effective in FAP patients in the prevention of colonic polyps, it may also be of benefit to the larger population of patients with sporadic colorectal adenomatous polyps who are also at risk of colorectal cancer.

Colorectal polyps are thought, at least in part, to arise from an imbalance in the levels of cell proliferation and apoptosis (natural cell death) in the colonic mucosa. It has been suggested that omega-3 polyunsaturated fatty acids (PUFAs) in fish oil can manipulate the high levels of colonic-mucosal cell proliferation rates associated with colonic adenomas.

The rationale for this trial is based on the increasing evidence linking inflammatory processes and the development of a number of cancers, including bowel cancer. This has focused attention on the role of inflammatory mediators in the development of cancer. In particular, the family of eicosanoids (including 2-series prostaglandins, 4-series leukotrienes and thromboxanes) produced through conversion of the omega-6 PUFA, arachidonic acid, via cyclo-oxygenase-2 (COX-2) is believed to contribute to the physiological processes of inflammation and the development of tumours. Prostaglandin E2, a product of the conversion of arachidonic acid via the COX-2 pathway, has been implicated in tumourigenesis through:

1. promotion of angiogenesis
2. anti-apoptotic properties
3. increasing expression of matrix metalloproteinases and hence the ability of a tumour cell to undergo metastasis
4. altering the cytokine expression profile of cells.

The class of eicosanoid synthesised will depend on the PUFA substrate. Whilst arachidonic acid is converted to 2-series prostaglandins and 4-series leukotrienes, EPA is converted to 3-series prostaglandins and 5-series leukotrienes. Overall, the latter eicosanoids are less potent as inflammatory mediators than those derived from arachidonic acid.

Increasing daily intake of EPA, the omega-3 PUFA analogue of arachidonic acid, alters the balance between the cell content of these fatty acids. This results in reduced production of the more active inflammatory/tumourigenic products of arachidonic acid metabolism. This is supported by the results of recent work at St George's Hospital Medical School, London. In patients with a history of colonic adenomas, daily dosing with a highly purified, free-fatty acid form of the EPA produced a significant reduction in cell proliferation and increase in apoptosis in the colonic mucosa. This preparation of EPA has the proprietary name "Alfa" and is referred to here as EPA.

This proposed study will be based upon the randomised, placebo-controlled National Cancer Institute sponsored study in which three groups of FAP patients were assigned to one of two doses of celecoxib (a COX-2 inhibitor) or placebo. The results showed a reduction in the polyp burden of the group taking the higher (400mg twice daily (bd)) dose. However, there is evidence to suggest that COX-2 inhibitors carry significant potential for side-effects. Adopting a similar design, EPA will be substituted for celecoxib in this randomised, placebo-controlled trial, comparing 2g EPA to placebo, with reduction in polyp burden as the primary objective.

Chemoprevention Trial in Familial Adenomatous Polyposis (FAP) Coli Using EPA

A Two-Arm Chemoprevention Trial in Familial Adenomatous Polyposis (FAP) Coli Patients Using the Purified Free Fatty Acid, Eicosapentaenoic Acid

Absolute change in the number of polyps measured in a defined focal area of the rectum.

Percentage change in the number of polyps measured in the defined focal area of the rectum in subjects treated with EPA compared to subjects receiving placebo.

Change in global rectal polyp burden in subjects treated with Eicosapentanoic Acid (EPA) compared to subjects receiving placebo. Each reviewer in the Polyp Video Scoring Committee assessed global colorectal polyp burden change as "better", "same as" or "worse". The qualitative assessment was assigned a score of +1 for "better", 0 for "same as" and -1 for "worse". Thereafter a mean overall reviewers score was calculated.

Relative EPA concentration of total free fatty acids in the rectal mucosa of subjects with FAP.

Incidence of adverse events in each treatment group.

S.L.A. Pharma AG

Eicosapentanoic Acid (EPA): 2 x 500mg EPA capsules twice daily for 6 months

Endoscopy: With video and photographs at baseline and month 6.

Biopsies taken: 9 biopsies taken at baseline and month 6 from the rectum of normal mucosa for analysis of apoptosis (3 biopsies), cell proliferation (3 biopsies) and mucosal fatty acid levels (3 biopsies). Two biopsies taken at baseline and month 6 from polyps for cell proliferation (1 biopsy) and apoptosis (1 biopsy).

2g/Day Eicosapentanoic Acid (EPA)

Medium chain triglycerides 2 capsules twice daily for six months.

Endoscopy: With video and photographs at baseline and month 6.

Biopsies taken: 9 biopsies taken at baseline and month 6 from the rectum of normal mucosa for analysis of apoptosis (3 biopsies), cell proliferation (3 biopsies) and mucosal fatty acid levels (3 biopsies). Two biopsies taken at baseline and month 6 from polyps for cell proliferation (1 biopsy) and apoptosis (1 biopsy).

2g/Day EPA

Total

Age, Continuous

Age, Categorical

Sex: Female, Male

United Kingdom

Region of Enrollment

The baseline characteristics are presented for the full analysis set which constitutes 55 of the 58 randomised subjects. The full analysis set includes all subjects who were randomised into the study, took at least one dose of study medication provided both at baseline and at least one treatment measurement for efficacy.

Dr Chris Jordan

Eicosapentaenoic Acid (EPA) 2g per day for six months

2g/Day Eicosapentaenoic Acid (EPA)

Medium chain triglycerides 2g per day for six months

13 subjects lacked the photographs required for counting the measurements of polyps. Reasons for lack of photographs varied including failure of video equipment, inability to identify identical views of the focal area and no forceps visible for calibration.

Absolute Change in the Number of Polyps Measured in a Focal Area of the Rectum.

Percentage Change in the Number of Polyps Measured in the Defined Focal Area of the Rectum.

5 subjects in the full analysis set lacked the video required for determining global rectal polyp burden due to failure of equipment.

Change in Global Rectal Polyp Burden.

3 subjects in the full analysis set had no samples for analysis.

Relative EPA Concentration of Total Free Fatty Acids in the Rectal Mucosa.

Number of Subjects With Adverse Events.

Medium chain triglycerides 2 g per day for six months.

Overall Study

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Celecoxib

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Observation of subjects treated with routine medical care

Routine Medical Care

Pfizer CT.gov Call Center

This is a registry-based observational study assessing clinical outcomes in FAP patients receiving celecoxib compared with historical/concurrent registry patients who have not received celecoxib.

Both retrospective and prospective data will be utilized. No sampling methods apply.

The study prematurely discontinued on April 11, 2008 due to slow enrollment. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.

Observational Familial Adenomatous Polyposis Registry Study In Patients Receiving Celecoxib Compared to Control Patients

A Registry-Based Observational Study Assessing Clinical Outcomes In Familial Adenomatous Polyposis In Patients Receiving Celecoxib (Celebrex(Registered), Onsenal(Registered)) Compared With Control Patients

Time(months): \[date of first excisional polypectomy of rectal polyp post IRA minus date of prior IRA plus 1\] divided by 30.44. Baseline = start of study follow-up: start of on-study celecoxib treatment period for celecoxib-treated subjects and comparable to index date for control subjects. Index date calculated as Matched Celecoxib-treated patients: number of days from most recent FAP-related surgery (IRA or IPAA) to start of study follow-up; add this number of days to matched control patient's most recent FAP-related surgery date=index date for Matched Control.

Time(months): \[date of first excisional polypectomy of rectal polyp post IRA minus date of start of study follow-up plus 1\] divided by 30.44.

Time (months): \[date of first excisional polypectomy of a rectal polyp post IPAA minus date of prior IPAA plus 1\] divided by 30.44. Baseline = start of study follow-up: start of on-study celecoxib treatment period for celecoxib-treated subjects and comparable to index date for control subjects. Index date calculated as Matched Celecoxib-treated patients: number of days from most recent FAP-related surgery (IRA or IPAA) to start of study follow-up; add this number of days to matched control patient's most recent FAP-related surgery date=index date for Matched Control.

Time (months): \[date of first excisional polypectomy of rectal polyp post IPAA minus date of start of study follow-up plus 1\] divided by 30.44.

Time (months): \[date of first excisional or ablational event for colonic, pouch, or duodenal adenomas occuring after date of most recent prior FAP-related surgical event or date of FAP diagnosis minus date of most recent prior FAP-related surgical event or date of FAP diagnosis plus 1\] divided by 30.44.

Time (months): \[date of first excisional or ablational event for colonic, pouch, or duodenal adenomas, occurring after date of most recent prior FAP-related surgical event, or date of FAP diagnosis minus date of start of study follow-up plus 1\] divided by 30.44.

Time (months): \[date of first FAP-related adverse event, occurring after the date of most recent prior FAP-related surgery, or date of FAP diagnosis minus date of most recent prior FAP-related surgery, or date of FAP diagnosis plus 1\] divided by 30.44. FAP-related adverse event defined as any FAP related cancers, desmoid tumors requiring procedural intervention, hospitalizations or procedural interventions, or death related to FAP (i.e., as a consequence of FAP, FAP complications, or a procedure or drug used to treat FAP-related medical problems).

Time (months): \[date of first FAP-related adverse event, occurring after the date of the most recent prior FAP-related surgery, or date of FAP diagnosis minus date of start of study follow-up plus 1\] divided by 30.44. FAP-related adverse event defined as any FAP related cancers, desmoid tumors requiring procedural intervention, hospitalizations or procedural interventions, or death related to FAP (i.e., as a consequence of FAP, FAP complications, or a procedure or drug used to treat FAP-related medical problems).

Time (months): \[date of IPAA minus date of prior IRA plus 1\] divided by 30.44.

Time (months): \[date of IPAA minus date of start of study follow-up plus 1\] divided by 30.44.

Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: Spigelman stage provides index of disease severity based on number of polyps, polyp size, histology, and dysplasia; range is Stage 0 (none) to Stage IV (severe). EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline). Spigelman Stage not completed as staging data largely missing; see measure: Duodenal adenoma burden as measured by polyp counts.

Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: attenuated: \<100 polyps, mild: between 100 to 1000 polyps, severe: \>1000 polyps. EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline).

Pfizer

Director, Clinical Trial Disclosure Group

All SAEs, expected and unexpected, occurring while subject was receiving celecoxib during his/her prospective (on-study) participation in the study, regardless of the apparent relationship to the drug, were collected and reported to the sponsor. Not applicable to Matched Control subjects n=13; SAEs not collected if no celecoxib treatment received.

All celecoxib treated subjects (includes Matched Celecoxib Treated and Not Matched Celecoxib Treated subjects); treatment prescribed outside clinical trial setting per routine medical care. Routine medical care: celecoxib is prescribed in the usual manner in accordance with the terms of the marketing authorization and as prescribed in medical practice. The assignment of the patient to celecoxib is not decided in advance by the study protocol but falls within current practice. All patients regardless of treatment status are followed according to local standard of medical care by the respective physicians.

All Celecoxib Treated

Celecoxib treatment prescribed outside clinical trial setting per routine medical care; matched to control subjects. Routine medical care: celecoxib is prescribed in the usual manner in accordance with the terms of the marketing authorization and as prescribed in medical practice. The assignment of the patient to celecoxib is not decided in advance by the study protocol but falls within current practice. All patients regardless of treatment status are followed according to local standard of medical care by the respective physicians.

Matched Celecoxib Treated

Observation of subjects not treated with celecoxib and followed according to routine medical practice; matched to matched celecoxib treated subjects. Routine medical practice: all patients regardless of treatment status are followed according to local standard of medical care by the respective physicians.

Matched Control

Celecoxib treatment prescribed outside clinical trial setting per routine medical care; not matched to control subjects. Routine medical care: celecoxib is prescribed in the usual manner in accordance with the terms of the marketing authorization and as prescribed in medical practice. The assignment of the patient to celecoxib is not decided in advance by the study protocol but falls within current practice. All patients regardless of treatment status are followed according to local standard of medical care by the respective physicians.

Not Matched Celecoxib Treated

<25 years

25 to 34 years

35 to 44 years

45 to 54 years

55 to 64 years

>64 years

Age not available (no surgery)

Age range groups at most recent FAP-related surgery (years). Prior to start of study follow-up = prior to baseline. Start of study follow-up: start of on-study celecoxib treatment period for celecoxib-treated subjects and index date for control subjects = baseline.

Age, Customized

Study prematurely discontinued May 2008 prior to reaching enrollment target; due to limited number of matched pairs, results do not provide sufficient data to evaluate effectiveness of celecoxib. Last subject last visit was November 2008.

Pfizer ClinicalTrials.gov Call Center

Time to FAP-related surgical events (months); twenty-fifth (25th) percentile presented due to limited number of subjects.

Index date based on most recent colon and or rectum adenomatous polyps evaluation, most recent duodenal adenomatous polyps evaluation, and most recent desmoids tumors evaluation for Matched Control, Not Matched Celecoxib, and All Celecoxib Treated, respectively.

Only 13 matched pairs identified: p-values not computed in analysis of time-to-event endpoints

Time to FAP-related surgical events (months); 25th percentile.

Observation of subjects not treated with celecoxib and followed according to routine medical practice; matched to matched celecoxib treated subjects. Routine medical practice: All patients regardless of treatment status are followed according to local standard of medical care by the respective physicians.

All eligible subjects with IRA performed prior to start of study follow-up; first excisional polypectomy of rectal polyp post IRA. Polyp size unavailable for many subjects; not considered in analysis.

Time From Ileorectal Anastomosis (IRA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IRA

All eligible subjects with IRA performed prior to start of study follow-up included, except left-censored subjects (had first excisional polypectomy of rectal polyp post IRA prior to start of study follow-up). No control group subjects (n=3) had a post-IRA polypectomy (no data).

Time From Start of Study Follow-up to the Time of First Excisional Polypectomy of a Rectal Polyp Post IRA

Time to FAP-related surgical events (months); 25th percentile. Index date based on most recent colon and or rectum adenomatous polyps evaluation, most recent duodenal adenomatous polyps evaluation, and most recent desmoids tumors evaluation for Matched Control, Not Matched Celecoxib, and All Celecoxib Treated, respectively.

All eligible subjects with IPAA performed prior to start of study follow-up included and with first excisional polypectomy of a rectal polyp post IPAA. No control group subjects (n=7) had a post-IPAA polypectomy (no data).

Time From Ileopouch Anal Anastomosis (IPAA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA

All eligible subjects with IPAA performed prior to start of study follow-up included, except left-censored subjects (had first excisional polypectomy post IPAA prior to start of study follow-up). No control group subjects (n=7) had a post-IPAA polypectomy (no data).

Time From Start of Study Follow-up to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA

All eligible subjects; first excisional or ablational event for rectal adenomas that does not qualify for primary efficacy endpoint; after most recent FAP-related surgical event prior to start of study follow-up or onset of FAP phenotype for subjects with no prior FAP-related surgery.

Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas (Duodenal Adenomatous Polyps)

All eligible subjects included, except left censored subjects (had any excisional or ablational event for rectal, colonic, pouch, or duodenal adenomas between date of most recent FAP-related surgical event performed prior to the start of study follow-up, or onset of FAP phenotype \[with no prior FAP-related surgery\], and start of study follow-up).

Time From Start of Study Follow-up to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas

Time to FAP-related events (months); 25th percentile.

All eligible subjects; first FAP-related adverse event (FAP-related cancers, desmoid tumors requiring procedural intervention, hospitalizations, procedural interventions, or death related to FAP) after subject's most recent FAP-related surgical event performed prior to start of study follow-up, onset of FAP phenotype (no prior FAP-related surgery).

Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First FAP-related Adverse Event

All eligible subjects included, except left-censored subjects (had any FAP-related adverse event between the date of most recent FAP-related surgical event performed prior to start of study follow-up, or onset of FAP phenotype (no prior FAP-related surgery), and start of study follow-up.

Time From Start of Study Follow-up to Time of First FAP-related Adverse Event

All eligible subjects with IRA performed prior to start of study follow-up; data censored (n=5) for control group subjects (no data).

Time From Post IRA to Time of Conversion From IRA to IPAA

All eligible subjects with IRA performed prior to start of study follow-up included, except left-censored subjects (had IPAA prior to start of study follow-up); data censored (n=5) for control group subjects (no data).

Time From Start of Study Follow-up to Time of Conversion From IRA to IPAA

Baseline attenuated

Baseline mild

Baseline severe

Baseline unknown

Baseline no polyps

Baseline not assessed

Post-baseline attenuated

Post-baseline mild

Post-baseline severe

Post-baseline unknown

Post-baseline no polyps

Post-baseline not assessed

EOS attenuated

EOS mild

EOS severe

EOS unknown

EOS no polyps

EOS not assessed

Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: attenuated: \<100 polyps, mild: between 100 to 1000 polyps, severe: \>1000 polyps. EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline). Post-hoc analysis of duodenal polyp burden in terms of severity categories and based on polyp numbers; Spigelman Stage not completed as staging data largely missing (see: Duodenal adenoma burden as measured by Spigelman Stage)

All subjects; Spigelman Stage not completed as staging data largely missing; duodenal polyp burden analyzed in terms of severity categories and based on polyp numbers.

Duodenal Adenoma Burden as Measured by Polyp Counts

All subjects; Spigelman Stage not completed as staging data largely missing.

Duodenal Adenoma Burden as Measured by Spigelman Stage

All subjects; duodenal polyp burden analyzed in terms of severity categories and based on polyp numbers.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemoprevention Trial in Familial Adenomatous Polyposis (FAP) Coli Using EPA	NCT00510692	Familial Adenom... FAP	Eicosapentanoic... Endoscopy Biopsies taken Placebo	18 Years -	S.L.A. Pharma AG
Chemoprevention Trial in Familial Adenomatous Polyposis (FAP) Coli Using EPA	NCT00510692	Familial Adenom... FAP	Eicosapentanoic... Endoscopy Biopsies taken Placebo	18 Years -	S.L.A. Pharma AG
Observational Familial Adenomatous Polyposis Registry Study In Patients Receiving Celecoxib Compared to Control Patients	NCT00151476	Familial Adenom...	Celecoxib Routine Medical...	12 Years -	Pfizer

Spots Global Cancer Trial Database for ira

Every month we try and update this database with for ira cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ira

Every month we try and update this database with for ira cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ira cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.