Mesalamine administration to prevent development of colorectal cancer in Lynch syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska Institutet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

12 Aug 2021 → ongoing

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514765-19-01

EudraCT number

2019-003011-55

ClinicalTrials.gov

NCT04920149

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety, Efficacy

To test whether mesalamine (5-ASA) reduces the occurence of any colorectal neoplasia (both benign and malignant tumours) compared to placebo in Lynch syndrome (LS) patients as detected by any colonoscopy until the end of treatment (24 months + 3 months) and end of study

Conditions and MedDRA coding

Lynch syndrome, which is increasing the risk of developing colorectal cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Proven tumor-free (including patients in which the polyps are removed endoscopically) carriers of a germline pathologic mutation on one of the MMR genes including MLH1, MSH2 (including EpCAM) and MSH6
2. Male or female subjects with the age > 30 years
3. Females who have been post-menopausal more than one (1) year or females of childbearing potential using a highly efficient method of contraception with less than 1% failure rate (i.e. oral hormonal contraceptives, hormone implants, hormone injections, sterilization, hormonal or copper intrauterine device, sterilized/vasectomized partner, or diaphragm in combination with a condom, spermicide or birth control pills) or should agree to abstain from heterosexual activity during treatment period. Females of childbearing potential must have a negative pregnancy test at screening and randomization
4. Signed written informed consent prior to inclusion in the study

Exclusion criteria 16

1. Presence of colorectal endoscopically non-removable malign neoplasia (patient can be included if the adenoma is removed)
2. Carriers of germline mutations in PMS2
3. Patients with history of stage 3 and 4 colorectal cancer (CRC) are excluded
4. Presence of any metastatic disease
5. Regular use of acetylsalicylic acid (ASA or aspirin): daily use of ≥100mg in more than 3 continuous months within the last year
6. Regular use of NSAIDs or COX-2 inhibitors: daily use in more than 3 continuous months within the last year
7. Hypersensitivity to 5-ASA
8. Patients after any subtotal or total colectomy
9. Colorectal surgery within the previous 6 months
10. Unwillingness to participate or who is considered unable to give an informed consent
11. Pregnant or breastfeeding women
12. Participation in another clinical study investigating another IMP within 3 months prior to screening
13. Renal insufficiency (GFR <30ml/min/1.73m2)
14. Severe liver disease or liver failure (elevation of liver enzymes above 3xULN)
15. Current or history of serious psychiatric disorder or alcohol/drug abuse that in the opinion of the investigator may impact the assessment of IMP safety and efficacy or protocol adherence
16. Prior history of myocarditis or pericarditis. Other severe acute or chronic medical condition (such as severe chronic lung (COPD, including asthma), kidney or heart diseases), duodenal ulcer, haemorrhagic diathesis or psychiatric condition or other abnormal clinical sign or laboratory abnormality that may increase the risk associated with study participation or ability to comply with study procedures, IMP administration and, in the judgment of the investigator, would make the subject inappropriate for entry into this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of any colorectal neoplasia (both benign and malignant tumors)

Secondary endpoints 4

1. The number of colorectal neoplasia (both benign and malignant tumors) per patient
2. The tumor progress in the 4 ordered stages
3. The dependence of treatment effects on history of colorectal cancer, sex and patients age (<45 years and ≥45 years)
4. Safety data are described and compared between groups in an exploratory manner

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska Institutet

Sponsor organisation

Karolinska Institutet

Address

Alfred Nobels Alle 8, Flemingsberg Flemingsberg

City

Huddinge

Postcode

141 52

Country

Sweden

Scientific contact point

Organisation

Karolinska Institutet

Contact name

Ann-Sofie Backman

Public contact point

Organisation

Karolinska Institutet

Contact name

Ann-Sofie Backman

Third parties 1

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications