Colorectal CancerPhase 2MesaCAPPNCT03070574
Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome
A Phase 2 study testing mesalamine 2400 MG (5-ASA) and mesalamine 1200 MG in people with Colorectal Cancer, run by Christoph Gasche at 6 sites in 6 countries.
Trial summary
Multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine, 1200mg mesalamine or placebo for prevention of colorectal neoplasia in Lynch Syndrome patients for 2 years. Read more about this study
- Who is it for?
- Ages 25 years and olderHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- mesalamine 2400 MG (5-ASA) and mesalamine 1200 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 24 Nov 2017to 10 Apr 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- Male or female subjects with the age > 25 years
- 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 before randomization.
- Signed written informed consent prior to inclusion in the study
Who cannot join
- Presence of colorectal endoscopically non-removable benign neoplasia (patient can be included if the adenoma is removed)
- Carriers of germline mutations in PMS2
- Patients with history of stage 3 and 4 colorectal cancer (CRC) are excluded
- Presence of metastatic disease
- Regular use of acetylsalicylic acid (ASA or aspirin): daily use of ≥100mg in more than 3 continuous months within the last year
- Regular use of NSAIDs or COX-2 inhibitors: daily use in more than 3 continuous months within the last year
Show all 16Show fewer
- Hypersensitivity to 5-ASA
- Patients after total or subtotal colectomy
- Colorectal surgery within the previous 6 months
- Unwillingness to participate or who is considered incompetent to give an informed consent
- Pregnant or breastfeeding women
- Participation in another clinical study investigating another IMP within 3 months prior to screening
- Renal insufficiency (GFR <30ml/min/1.73m2)
- Severe liver disease or liver failure (elevation of liver enzymes above 3xULN)
- 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 andefficacy or protocol adherence
- 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) or psychiatric condition 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
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
Germany1 site
HELIOS Universitätsklinikum Wuppertal, Zentrum für Hereditäre Tumorerkrankungen
Wuppertal, North Rhine-Westphalia, 42883
Israel1 site
Rabin Medical Center Beilinson Hospital Gastroenterology Department
Petah Tikva, 4941492
Poland1 site
Department of Genetics and Pathomorphology of Pomeranian Medical University
Szczecin, 71-252
Sweden1 site
Karolinska universitetsjukhuset, A6:00 Gastroenterologiskt öppenvårdscentrum, Mottagningen för ärftlig tarmcancer
Solna, 17176
About this study
Official title: Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome - MesaCAPP
Multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine, 1200mg mesalamine or placebo for prevention of colorectal neoplasia in Lynch Syndrome patients for 2 years.
Read the detailed description
This is a multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine (5-ASA), 1200mg mesalamine (5-ASA) or placebo in LS patients for a 2-year treatment. 540 tumor free carriers of a known genetic mutation in a major MMR gene (including patients in which the polyps are endoscopically removed) will be randomized 1:1:1 (180 each) to receive 2400mg mesalamine, 1200mg mesalamine or placebo. Patients will be identified through local or national registries and through collaboration with sites. Tumor free patients, assessed by white light high resolution colonoscopy, will be randomized to the study. A serum and stool sample will be taken to identify for mesalamine compliance and potential biomarkers. Biopsies of the normal tissue of ascending colon and rectum will be taken at the first and the last colonoscopy.
The aim of the study is to investigate the effect of regular treatment with mesalamine (5-ASA) on the occurrence of any colorectal neoplasia, tumor multiplicity (the number of detected adenomas/carcinomas) and tumor progression in LS patients.
A 50% reduction of the occurrence of colorectal neoplasia in mesalamine-treated patients is expected. Tumor multiplicity and tumor progression (severity of the neoplastic lesions) will be investigated.
- Conditions
- Colorectal Cancer
- Being tested
- mesalamine 2400 MG (5-ASA), mesalamine 1200 MG, Placebo
- Keywords
- Lynch Syndrome, Chemoprevention, Mesalazine, 5-ASA
- Medical subject headings
- Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mesalamine 2400 MG (5-ASA)Drug
Also called Mezavant, Mesalazine, 5-aminosalicylic acid (5-ASA)
For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers, each 1200mg of IMP (= 2400 mg), every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.
mesalamine 1200 MGDrug
Also called Mezavant, Mesalazine, 5-aminosalicylic acid (5-ASA)
For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (1200 mg/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.
PlaceboOther
For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (placebo/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.
| Study group | Role | What they receive |
|---|---|---|
| 2400 MG mesalamine (5-ASA) total | Experimental | 2400mg (1200mg mesalamine/1200mg) mesalamine once daily in the morning for the treatment phase of the study (24 months) Receives: Drug: mesalamine 2400 MG (5-ASA) |
| 1200 MG mesalamine (5-ASA) total | Experimental | placebo/1200mg mesalamine once daily in the morning for the treatment phase of the study (24 months) Receives: Drug: mesalamine 1200 MG; Other: Placebo |
| Placebo | Placebo comparator | placebo/placebo once daily in the morning for the treatment phase of the study (24 months) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in the occurrence of any colorectal neoplasia in LS patients
- Occurrence of any colorectal neoplasia (both benign and malignant tumors) between groups is described by absolute frequencies and percentages with 95 % confidence intervals. A logistic regression is used to assess differences between active treatment and placebo for the occurrence of any colorectal neoplasia, adjusted for country and history of cancer before randomization. Treatment effects are assessed by odds-ratios and corresponding 95 % confidence intervals.
Measured: End of treatment at 24 months +/- 1 month
Reduction in the occurrence of any colorectal neoplasia in LS patients
As above
Measured: End of study at year 6 +/- 3 months
Secondary outcomes (5)
Tumor multiplicity
The number of colorectal neoplasia (both benign and malignant tumors) per patient will be tested between groups by an analysis of variance, adjusting for country and history of cancer before randomization. In case of non-normally distributed residuals a suitable transformation to achieve normal distribution is considered.
It will be tested whether 5-ASA (low- and high-dose together) reduces the number of any colorectal neoplasia (both benign and malignant tumors; tumor multiplicity) compared to placebo in LS patients at the end of treatment and end of study. Advanced adenomas are defined by a diameter above 1 cm villous or tubulo-villous histology or high grade dysplasia.
All tests are two-sided and a significance level of 5 % is used.
Measured: End of treatment at 24 months +/- 1 month
Tumor progress
The tumor progress in 4 ordered stages will be tested between groups by a chi-square trend test stratified for country and history of cancer before randomization and modelled by an ordinal logistic regression.
It will be tested whether 5-ASA (low- and high-dose together) reduces tumor progression (compared 4 ordinal stages: no colorectal neoplasia / non-advanced adenoma / advanced adenoma / carcinoma) compared to placebo in LS patients at the end of treatment and end of study. Advanced adenomas are defined by a diameter above 1 cm villous or tubulo-villous histology or high grade dysplasia.
All tests are two-sided and a significance level of 5 % is used.
Measured: End of treatment at 24 months +/- 1 month
Treatment effects
The dependence of treatment effects on history of colorectal cancer, sex and patients age (<45 years and ≥45 years) will be assessed by modelling interactions between these factors and treatment in the corresponding regression models.
If differences between 5-ASA (low- and high-dose together) effects and placebo effects on the occurrence of colorectal neoplasia, tumor multiplicity or tumor progression depend on the history of colorectal cancer, sex and patients age (LS patients below 45 years of age or 45 years of age and older) will be investigated.
All tests are two-sided and a significance level of 5 % is used.
Measured: End of treatment at 24 months +/- 1 month
High and low dose ASA
Differences between high and low dose ASA for the occurrence of colorectal neoplasia, tumor multiplicity and tumor progression will be analysed by the same methods as for the comparison between ASA and placebo to investigate differences between low and high dose 5-ASA with respect to the occurrence of colorectal neoplasia, to tumor multiplicity and tumor progression.
All tests are two-sided and a significance level of 5 % is used.
Measured: End of treatment at 24 months +/- 1 month
Significant findings & illnesses - adverse events
Safety data are described and compared between groups in an exploratory manner to determine the safety concerning 5-ASA in LS patient. Therefore significant findings/illnesses, reported after the start of the study and which meet the definition of an AE, will be recorded in the CRF.
Intention to treat set: This analysis set includes subjects who were randomized (and received at least one dose study drug). This analysis set will be chosen for safety assessment.
All tests are two-sided and a significance level of 5 % is used.
Measured: End of treatment at 24 months +/- 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start24 Nov 2017
- Primary completion10 Apr 2019
- Study completion10 Apr 2019
Why it stopped: Due to poor patient recruitment and insufficient financing.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christoph Gasche
- Sponsor type
- University, hospital or other
- Collaborators
- Prof. Dr. Gabriela Möslein, Germany, Prof. Dr. Hans Vasen, The Netherlands, Prof. Dr. med. Jan Lubinski, Poland, Prof. Dr. med. Yaron Niv, Israel, Univ. Prof. Dr. Judith Karner-Hanusch, Austria, Ann-Sofie Backman, MD PhD, Sweden
- Responsible party
- Sponsor-investigator, Christoph Gasche, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03070574
- Sponsor's protocol ID
- MesaCAPP
- Acronym
- MesaCAPP
- Status last verified
- Apr 2019
- First submitted
- 22 Feb 2017
- Last updated
- 18 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome - MesaCAPP
- ClinicalTrials.gov ID
- NCT03070574
- Acronym / sponsor ID
- MesaCAPP / MesaCAPP
- Conditions
- Colorectal Cancer
- Keywords
- Lynch Syndrome, Chemoprevention, Mesalazine, 5-ASA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to poor patient recruitment and insufficient financing.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Christoph GascheUniversity, hospital or other
- Collaborators
- Prof. Dr. Gabriela Möslein, Germany, Prof. Dr. Hans Vasen, The Netherlands, Prof. Dr. med. Jan Lubinski, Poland, Prof. Dr. med. Yaron Niv, Israel, Univ. Prof. Dr. Judith Karner-Hanusch, Austria, Ann-Sofie Backman, MD PhD, Sweden
- Study start
- 24 Nov 2017 (actual)
- Primary completion
- 10 Apr 2019 (actual)
- Study completion
- 10 Apr 2019 (actual)
- First posted
- 3 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine, 1200mg mesalamine or placebo for prevention of colorectal neoplasia in Lynch Syndrome patients for 2 years.
Detailed description
This is a multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine (5-ASA), 1200mg mesalamine (5-ASA) or placebo in LS patients for a 2-year treatment. 540 tumor free carriers of a known genetic mutation in a major MMR gene (including patients in which the polyps are endoscopically removed) will be randomized 1:1:1 (180 each) to receive 2400mg mesalamine, 1200mg mesalamine or placebo. Patients will be identified through local or national registries and through collaboration with sites. Tumor free patients, assessed by white light high resolution colonoscopy, will be randomized to the study. A serum and stool sample will be taken to identify for mesalamine compliance and potential biomarkers. Biopsies of the normal tissue of ascending colon and rectum will be taken at the first and the last colonoscopy.
The aim of the study is to investigate the effect of regular treatment with mesalamine (5-ASA) on the occurrence of any colorectal neoplasia, tumor multiplicity (the number of detected adenomas/carcinomas) and tumor progression in LS patients.
A 50% reduction of the occurrence of colorectal neoplasia in mesalamine-treated patients is expected. Tumor multiplicity and tumor progression (severity of the neoplastic lesions) will be investigated.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 2400 MG mesalamine (5-ASA) total | Experimental | Drug: mesalamine 2400 MG (5-ASA)2400mg (1200mg mesalamine/1200mg) mesalamine once daily in the morning for the treatment phase of the study (24 months) |
| 1200 MG mesalamine (5-ASA) total | Experimental | Drug: mesalamine 1200 MG, Other: Placeboplacebo/1200mg mesalamine once daily in the morning for the treatment phase of the study (24 months) |
| Placebo | Placebo comparator | Other: Placeboplacebo/placebo once daily in the morning for the treatment phase of the study (24 months) |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
- Male or female subjects with the age > 25 years
- 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 before randomization.
- Signed written informed consent prior to inclusion in the study
Key exclusion criteria (16 listed)
- Presence of colorectal endoscopically non-removable benign neoplasia (patient can be included if the adenoma is removed)
- Carriers of germline mutations in PMS2
- Patients with history of stage 3 and 4 colorectal cancer (CRC) are excluded
- Presence of metastatic disease
- Regular use of acetylsalicylic acid (ASA or aspirin): daily use of ≥100mg in more than 3 continuous months within the last year
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mesalamine 2400 MG (5-ASA)Also: Mezavant, Mesalazine, 5-aminosalicylic acid (5-ASA)For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers, each 1200mg of IMP (= 2400 mg), every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally. | Drug | 2400 MG mesalamine (5-ASA) total |
| mesalamine 1200 MGAlso: Mezavant, Mesalazine, 5-aminosalicylic acid (5-ASA)For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (1200 mg/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally. | Drug | 1200 MG mesalamine (5-ASA) total |
| PlaceboFor this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (placebo/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally. | Other | 1200 MG mesalamine (5-ASA) total, Placebo |
Primary outcome
Reduction in the occurrence of any colorectal neoplasia in LS patients
Time frame: End of treatment at 24 months +/- 1 month
• Occurrence of any colorectal neoplasia (both benign and malignant tumors) between groups is described by absolute frequencies and percentages with 95 % confidence intervals. A logistic regression is used to assess differences between active treatment and placebo for the occurrence of any colorectal neoplasia, adjusted for country and history of cancer before randomization. Treatment effects are assessed by odds-ratios and corresponding 95 % confidence intervals.
Reduction in the occurrence of any colorectal neoplasia in LS patients
Time frame: End of study at year 6 +/- 3 months
As above
5 secondary outcomes
Tumor multiplicity
Time frame: End of treatment at 24 months +/- 1 month
Tumor progress
Time frame: End of treatment at 24 months +/- 1 month
Treatment effects
Time frame: End of treatment at 24 months +/- 1 month
High and low dose ASA
Time frame: End of treatment at 24 months +/- 1 month
Significant findings & illnesses - adverse events
Time frame: End of treatment at 24 months +/- 1 month
Results and safety
The study was stopped early (reason given: Due to poor patient recruitment and insufficient financing.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing mesalamine 2400 MG (5-ASA) and mesalamine 1200 MG in people with Colorectal Cancer, run by Christoph Gasche at 6 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Austria, Germany, Israel, Netherlands, Poland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to poor patient recruitment and insufficient financing.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in the occurrence of any colorectal neoplasia in LS patients (time frame: End of treatment at 24 months +/- 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2019.