Colon CancerDECONCT01882660
Pre-operative Decitabine in Colon Cancer: a Proof of Principle Study
A study testing Decitabine in people with Colon Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Background of the study: Colon cancer is the second leading cause of cancer-related death world wide. Although patients presenting with early disease (stage I-III) can be cured, prognosis varies from 90% in stage I to 50-80% in stage II and III. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer
- What is being tested?
- Decitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Jul 2013to Jan 2018
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy proven colon cancer or high suspicion of colon cancer on a previous endoscopy.
- Planned endoscopy.
- Age ≥ 18yr.
- ECOG/ WHO performance 0-2.
- Written informed consent.
- Patients with biopsy proven colon cancer who will undergo primary tumor resection.
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- Age ≥ 18yr.
- ECOG/ WHO performance 0-2.
- Adequate bone marrow function (ANC>1500/mm3, hemoglobin>9g/dL (which may be obtained by transfusions), platelets>100,000)
- Adequate hepatic function (AST and ALT <2.5x upper limit of normal (ULN)).
- Adequate renal function (Serum creatinine ≤1.5 x ULN or calculated creatinine of >50ml/min)
- Women of child-bearing age must be willing to use adequate contraception and have negative serum or urine pregnancy test within 3 days prior to registration.
- Written informed consent.
Who cannot join
- 1. Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol.
- In- and exclusion criteria second part:
- In order to participate in the second part of the study - treatment with decitabine - a subject must meet all of the following criteria:
- Known hypersensitivity to decitabine or its additives.
- Surgery not planned according to time frame of the study,
- Other systemic or local treatment of the primary tumor in the waiting time until surgery.
- Administration of any experimental drug within 60 days prior to the first dose of decitabine.
Trial locations and contacts
1 site in 1 country.
About this study
Background of the study: Colon cancer is the second leading cause of cancer-related death world wide.
Although patients presenting with early disease (stage I-III) can be cured, prognosis varies from 90% in stage I to 50-80% in stage II and III. Therefore, prevention of metastases after early disease is of utmost importance. Derepression of Wnt targets may provide a novel target for therapy.
Objectives: The primary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can increase Wnt target gene expression as measured in resected tumors compared to pretreatment biopsies. The secondary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can revert CpG methylation and induce more favorable tumor characteristics as measured in resected tumors compared to pretreatment biopsies. The tertiary objective is to compare changes in Wnt target gene expression, CpG methylation and tumor characteristics for Wnt methylated and nonmethylated tumors as measured in resected tumors compared to pretreatment biopsies and identify new stratification markers.
Read the detailed description
Rationale: Colon cancer is the second leading cause of cancer-related death world wide.
Although patients presenting with early disease (stage I-III) can be cured, prognosis varies from 90% in stage I to 50-80% in stage II and III. Therefore, prevention of metastases after early disease is of utmost importance. Extensive studies of the Wnt signal cascade have elucidated its role in colorectal cancer development and proliferation. Several well-known targets of the Wnt-cascade, like DKK1, APCDD1 and AXIN2, serve as feedback inhibitors and likely prevent pathway hyperactivation. Therefore, loss of these control mechanisms, for example due to repression of Wnt targets by CpG island methylation, serves as a potent proliferative signal. Recently, we identified a subset of colon cancers that are typified by CpG island methylation of specific Wnt target genes and have a poor prognosis. Moreover, in preclinical studies we showed that derepression of Wnt-targets by the demethylating agent decitabine resulted in tumor growth suppression. Thus, derepression of Wnt targets may provide a novel target for therapy. Objectives: The primary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can increase Wnt target gene expression as measured in resected tumors compared to pretreatment biopsies. The secondary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can revert CpG methylation and induce more favorable tumor characteristics as measured in resected tumors compared to pretreatment biopsies. The tertiary objective is to compare changes in Wnt target gene expression, CpG methylation and tumor characteristics for Wnt methylated and nonmethylated tumors as measured in resected tumors compared to pretreatment biopsies and identify new stratification markers.
Study design: Interventional study.
Study population:
Patients > 18 yr old with histopathologically proven or high suspicion of colon cancer.
Intervention: In patients with proven colon cancer, five extra biopsies will be taken from the tumour during endoscopy to determine CpG methylation of Wnt target genes in fresh tumor samples. Next, these patients will pre-operatively receive decitabine as a single intravenous infusion at a dose of 45 mg/m2 over 6 hr. After resection, Wnt target gene expression and CpG methylation of Wnt target genes will again be determined in fresh tumor samples.
Main study parameters: The primary study parameter is Wnt target gene expression (APCDD1, AXIN2, DKK1, LGR5 and ASCL2). Secondary study parameters are Wnt target and CIMP gene methylation, beta-catenin localization, proliferation (Ki-67), apoptosis (TUNEL and M30 assay) and tumor differentiation.
- Conditions
- Colon Cancer
- Being tested
- Decitabine
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
| Study group | Role | What they receive |
|---|---|---|
| Decitabine treatment | Experimental | Treatment with decitabine Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wnt target gene expression (APCDD1, AXIN2, DKK1, LGR5 and ASCL2)
The primary objective of the study is to assess whether short-course pre-operative treatment with the demethylating agent decitabine can increase Wnt target gene expression as measured in resected tumors compared to pretreatment biopsies in patients with primary colon cancer.
Measured: 30 minutes after surgery
Secondary outcomes (6)
Wnt target methylation.
The secondary objective of the study is to assess whether short-course pre-operative treatment with decitabine can revert CpG methylation and induce more favorable tumor characteristics as measured in resected tumors compared to pretreatment biopsies in patients with primary colon cancer.
Measured: 30 minutes after surgery
CIMP gene methylation
See above
Measured: 30 minutes after surgery
Beta-catenin localisation
See above
Measured: 30 minutes after surgery
Proliferation (Ki-67)
See above
Measured: 30 minutes after surgery
Apoptose (TNEL en M30 assay)
See above.
Measured: 30 minutes after surgery
Tumor differentiation
See above
Measured: 30 minutes after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2013 (estimated)
- Study startJul 2013
- Primary completionJan 2018
- Study completionJan 2018
Why it stopped: Inclusion of patients was slow. Could not reach the target within the studyperiod.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01882660
- Sponsor's protocol ID
- NL44048.018.13
- Acronym
- DECO
- Status last verified
- Dec 2022
- First submitted
- 24 May 2013
- Last updated
- 19 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-operative Decitabine in Colon Cancer: a Proof of Principle Study
- ClinicalTrials.gov ID
- NCT01882660
- Acronym / sponsor ID
- DECO / NL44048.018.13
- Conditions
- Colon Cancer
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inclusion of patients was slow. Could not reach the target within the studyperiod.
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Jul 2013
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 20 Jun 2013 (estimated)
- 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.
Background of the study: Colon cancer is the second leading cause of cancer-related death world wide.
Although patients presenting with early disease (stage I-III) can be cured, prognosis varies from 90% in stage I to 50-80% in stage II and III. Therefore, prevention of metastases after early disease is of utmost importance. Derepression of Wnt targets may provide a novel target for therapy.
Objectives: The primary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can increase Wnt target gene expression as measured in resected tumors compared to pretreatment biopsies. The secondary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can revert CpG methylation and induce more favorable tumor characteristics as measured in resected tumors compared to pretreatment biopsies. The tertiary objective is to compare changes in Wnt target gene expression, CpG methylation and tumor characteristics for Wnt methylated and nonmethylated tumors as measured in resected tumors compared to pretreatment biopsies and identify new stratification markers.
Detailed description
Rationale: Colon cancer is the second leading cause of cancer-related death world wide.
Although patients presenting with early disease (stage I-III) can be cured, prognosis varies from 90% in stage I to 50-80% in stage II and III. Therefore, prevention of metastases after early disease is of utmost importance. Extensive studies of the Wnt signal cascade have elucidated its role in colorectal cancer development and proliferation. Several well-known targets of the Wnt-cascade, like DKK1, APCDD1 and AXIN2, serve as feedback inhibitors and likely prevent pathway hyperactivation. Therefore, loss of these control mechanisms, for example due to repression of Wnt targets by CpG island methylation, serves as a potent proliferative signal. Recently, we identified a subset of colon cancers that are typified by CpG island methylation of specific Wnt target genes and have a poor prognosis. Moreover, in preclinical studies we showed that derepression of Wnt-targets by the demethylating agent decitabine resulted in tumor growth suppression. Thus, derepression of Wnt targets may provide a novel target for therapy. Objectives: The primary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can increase Wnt target gene expression as measured in resected tumors compared to pretreatment biopsies. The secondary objective of the study is to assess in patients with primary colon cancer whether short-course pre-operative treatment with decitabine can revert CpG methylation and induce more favorable tumor characteristics as measured in resected tumors compared to pretreatment biopsies. The tertiary objective is to compare changes in Wnt target gene expression, CpG methylation and tumor characteristics for Wnt methylated and nonmethylated tumors as measured in resected tumors compared to pretreatment biopsies and identify new stratification markers.
Study design: Interventional study.
Study population:
Patients > 18 yr old with histopathologically proven or high suspicion of colon cancer.
Intervention: In patients with proven colon cancer, five extra biopsies will be taken from the tumour during endoscopy to determine CpG methylation of Wnt target genes in fresh tumor samples. Next, these patients will pre-operatively receive decitabine as a single intravenous infusion at a dose of 45 mg/m2 over 6 hr. After resection, Wnt target gene expression and CpG methylation of Wnt target genes will again be determined in fresh tumor samples.
Main study parameters: The primary study parameter is Wnt target gene expression (APCDD1, AXIN2, DKK1, LGR5 and ASCL2). Secondary study parameters are Wnt target and CIMP gene methylation, beta-catenin localization, proliferation (Ki-67), apoptosis (TUNEL and M30 assay) and tumor differentiation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine treatment | Experimental | Drug: DecitabineTreatment with decitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Biopsy proven colon cancer or high suspicion of colon cancer on a previous endoscopy.
- Planned endoscopy.
- Age ≥ 18yr.
- ECOG/ WHO performance 0-2.
- Written informed consent.
Key exclusion criteria (7 listed)
- 1. Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol.
- In order to participate in the second part of the study - treatment with decitabine - a subject must meet all of the following criteria:
- Known hypersensitivity to decitabine or its additives.
- Surgery not planned according to time frame of the study,
- Other systemic or local treatment of the primary tumor in the waiting time until surgery.
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 |
|---|---|---|
| Decitabine | Drug | Decitabine treatment |
Primary outcome
Wnt target gene expression (APCDD1, AXIN2, DKK1, LGR5 and ASCL2)
Time frame: 30 minutes after surgery
The primary objective of the study is to assess whether short-course pre-operative treatment with the demethylating agent decitabine can increase Wnt target gene expression as measured in resected tumors compared to pretreatment biopsies in patients with primary colon cancer.
6 secondary outcomes
Wnt target methylation.
Time frame: 30 minutes after surgery
CIMP gene methylation
Time frame: 30 minutes after surgery
Beta-catenin localisation
Time frame: 30 minutes after surgery
Proliferation (Ki-67)
Time frame: 30 minutes after surgery
Apoptose (TNEL en M30 assay)
Time frame: 30 minutes after surgery
Tumor differentiation
Time frame: 30 minutes after surgery
Results and safety
The study was stopped early (reason given: Inclusion of patients was slow. Could not reach the target within the studyperiod.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Decitabine in people with Colon Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 13 inclusion and 7 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 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Inclusion of patients was slow. Could not reach the target within the studyperiod.). 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?
Wnt target gene expression (APCDD1, AXIN2, DKK1, LGR5 and ASCL2) (time frame: 30 minutes after surgery). 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 19 Dec 2022.