Condition category
Cancer
Date applied
18/05/2001
Date assigned
18/05/2001
Last edited
14/11/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.capp2.com

Contact information

Type

Scientific

Primary contact

Prof John Burn

ORCID ID

Contact details

CAPP Office
Bioscience Centre
Times Square
Scotswood Road
Newcastle upon Tyne
NE1 4EP
United Kingdom
+44 (0)191 2331414
John.Burn@ncl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

G0100496

Study information

Scientific title

Acronym

CAPP2

Study hypothesis

1. To study the effect of aspirin and/or resistant starch in a placebo controlled, double-blind randomised trial on carriers of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) (Lynch Syndrome);
2. To assess the polyp, adenoma and/or cancer recurrence in these patients during a two to four year treatment period.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Hereditary non-polyposis colorectal cancer (HNPCC)

Intervention

Targets Lynch syndrome patients/600 mg enteric coated aspirin daily or placebo AND 30 g resistant starch or placebo:
1. 600 mg aspirin/30 g treatment starch
2. 600 mg placebo tablets/30 g treatment starch
3. 600 mg aspirin/30 g placebo starch
4. 600 mg placebo tablets/30 g placebo starch

Intervention type

Drug

Phase

Not Specified

Drug names

Aspirin and resistant starch

Primary outcome measures

The primary endpoint will be the number, size and histological stage of colorectal carcinomas found after a minimum of 2 years treatment.

Secondary outcome measures

1. Adenoma size and number:
Elective removal of polyps will make fully developed cancers rare. The main outcome measure will be the number, size, location, villosity and dysplasia of adenomatous polyps
2. Apoptosis in adenomata:
A recent observation in the histology of an adenoma from a participant in CAPP1 has led us to consider that the pattern of apoptosis within adenomata is worthy of study. This is in keeping with the evidence in vivo and in vitro for an effect of aspirin on apoptosis. We will therefore request histopathological assessment of adenomas snared at colonoscopy, with special interest in signet cells and undifferentiated medullary carcinoma.
3. Cell proliferation and apoptosis in flat mucosa:
In a sub-set of participants, biopsies of flat rectal mucosa will be collected before and after treatment to test the hypothesis that altered cell proliferation (see Mills et al. 2001) and/or apoptosis is a reliable biomarker of tumorigenesis.
4. Other cancers:
Gene carriers of Lynch syndrome are at increased risk of many extracolonic cancers, and these will be systematically reported in the study group. In particular, there is a 42% lifetime risk of endometrial cancers in female gene carriers (Dunlop et al., 1997; Watson et al., 1994). These data are important in monitoring any favourable or unfavourable change in all cancers within the different study groups. In particular, it will be important to ascertain if the interventions might reduce colonic tumours while at the same time increasing upper gastrointestinal (GI) or non GI tumours. In mouse studies parallel to CAPP1, we have found a significant increase in small bowel polyps in APC knockout mice fed excess resistant starch (Burn et al., 1996). Aspirin reversed the effect. Regular aspirin use is associated with a reduced incidence of gastric cancer, a malignancy reported with increased frequency in Lynch syndrome families.

Overall trial start date

01/01/1999

Overall trial end date

31/01/2008

Reason abandoned

Eligibility

Participant inclusion criteria

A) Genetic diagnosis:
Proven carriers of pathological mutations in mismatch repair genes

B) Clinical diagnosis:
Belong to a recognised Lynch Syndrome family based on the modified Amsterdam criteria (see below) AND have had at least one of the following events:
1. A colorectal cancer
2. An adenoma of over 5 mm diameter
3. A related carcinoma; endometrial carcinoma is particularly predictive of gene carrier status but others include small bowel, uroepithelial, or stomach
4. An adenoma under 40 years of age
5. Two or more adenomas on more than one occasion
6. Also have had an intact colon or have had only a segmental resection and have normal bowel actions

Modified Amsterdam criteria:
1. Three cases of HNPCC related cancer in the family
2. One is a first degree relative of the other two
3. One under 50 years
4. At least two generations affected

All enrolees should also:
1. Be over 25 years old. There is no upper age limit.
2. Have intact colon or have had only a segmental resection and have normal (non-medicated) bowel actions (three or fewer formed bowel actions per day).

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1,000

Participant exclusion criteria

1. Pregnancy (note: there have been few reports of adverse effects associated with aspirin use in pregnancy and aspirin is not regarded as a teratogen so women of child bearing age may be recruited. However, women should temporarily withdraw from the trial if they become pregnant. They can restart immediately after delivery if they are not breast feeding. If mothers are breast feeding they should not re-enter the trial until they have completed breast feeding.)
2. Medical contraindications for aspirin e.g. aspirin induced asthma, previous aspirin/Non-Steroidal Anti-Inflammatory Drug (NSAID) induced peptic ulcer, renal impairment beyond creatinine of 0.15 mmol/l, or haemorrhagic diathesis
3. Already taking NSAIDs or steroids (note: if, during participation in the trial, a participant needs to take a course of NSAIDs they should be temporarily withdrawn from all limbs of the trial)
4. Severe intercurrent disease
5. Known to be Human Immunodeficiency Virus (HIV) positive (routine testing not required)

Recruitment start date

01/01/1999

Recruitment end date

31/01/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

CAPP Office
Newcastle upon Tyne
NE1 4EP
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne Hospitals NHS Trust (UK)

Sponsor details

R&D Department
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
+44 (0)191 282 5959
craig.mackerness@trvi.nuth.northy.nhs.uk

Sponsor type

Government

Website

Funders

Funder type

Research council

Funder name

Medical Research Council (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/19073976
2. 2012 aspirin results in http://www.ncbi.nlm.nih.gov/pubmed/22036019
3. 2012 resistant starch results in http://www.ncbi.nlm.nih.gov/pubmed/23140761

Publication citations

  1. Results

    Burn J, Bishop DT, Mecklin JP, Macrae F, Möslein G, Olschwang S, Bisgaard ML, Ramesar R, Eccles D, Maher ER, Bertario L, Jarvinen HJ, Lindblom A, Evans DG, Lubinski J, Morrison PJ, Ho JW, Vasen HF, Side L, Thomas HJ, Scott RJ, Dunlop M, Barker G, Elliott F, Jass JR, Fodde R, Lynch HT, Mathers JC, , Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome., N. Engl. J. Med., 2008, 359, 24, 2567-2578, doi: 10.1056/NEJMoa0801297.

  2. Aspirin results

    Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard ML, Dunlop MG, Ho JW, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJ, Vasen HF, Barker G, Crawford G, Elliott F, Movahedi M, Pylvanainen K, Wijnen JT, Fodde R, Lynch HT, Mathers JC, Bishop DT, , Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial., Lancet, 2011, 378, 9809, 2081-2087, doi: 10.1016/S0140-6736(11)61049-0.

  3. Resistant starch results

    Mathers JC, Movahedi M, Macrae F, Mecklin JP, Moeslein G, Olschwang S, Eccles D, Evans G, Maher ER, Bertario L, Bisgaard ML, Dunlop M, Ho JW, Hodgson S, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJ, Vasen H, Gerdes AM, Barker G, Crawford G, Elliott F, Pylvanainen K, Wijnen J, Fodde R, Lynch H, Bishop DT, Burn J, , Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial., Lancet Oncol., 2012, 13, 12, 1242-1249, doi: 10.1016/S1470-2045(12)70475-8.

Additional files

Editorial Notes