Pre-operative Decitabine in Colon Cancer: a proof of principle study

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 88

Inclusion Criteria

In order to participate in the first part of the study, determination of methylation status on tumor biopsies, a subject must meet all of the following criteria:
1. Biopsy proven colon cancer or high suspicion of colon cancer.
2. Age >= 18yr.
3. Written informed consent.;In order to participate in the second part of the study - treatment with decitabine - a subject must meet all of the following criteria:
1. Patients with biopsy proven colon cancer who will undergo primary tumor resection.
2. Age >= 18yr.
3. ECOG/ WHO performance 0-2.
4. Adequate bone marrow function (ANC>1500/mm3, hemoglobin>9g/dL (which may be obtained by transfusions), platelets>100,000)
5. Adequate hepatic function (AST and ALT <2.5x upper limit of normal (ULN)).
6. Adequate renal function (Serum creatinine <=1.5 x ULN or calculated creatinine clearance of >50ml/min)
7. 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.
8. Written informed consent.;In order to participate part IIB of the study - obtaining tumor material - a subject must meet all of the following criteria:
1. Patients with biopsy proven colon cancer who will undergo primary tumor resection.
2. Age >= 18yr.
3. Karnofsky Performance Score 70.
4. Written informed consent.

Exclusion Criteria

A potential subject for the first part of the study - determination of methylation status on tumor biopsies - who meets any of the following criteria will be excluded from participation in this study:
1. Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol.;A potential subject for the second part of the study - treatment with decitabine - who meets any of the following criteria will be excluded from participation in this study:
1. Known hypersensitivity to decitabine or its additives.
2. Surgery not planned according to time frame of the study,
3. Other systemic or local treatment of the primary tumor in the waiting time until surgery.
4. Administration of any experimental drug within 60 days prior to the first dose of decitabine.
5. Women of child-bearing age who are pregnant or lactating.
6. Sexual active males who have intercourse with women of child-bearing age and do not take adequate contraceptive measures.
7. Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol.;A potential subject for part IIB of the study - obtaining tumor material - who meets any of the following criteria will be excluded from participation in this study:
1. Surgery not planned according to time frame of the study
2. Other systemic or local treatment of the primary tumor in the waiting time until surgery.
3. Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary study parameter is Wnt target gene expression (APCDD1, AXIN2, DKK1,<br /><br>LGR5 and ASCL2). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary study parameters are Wnt target and CIMP gene methylation,<br /><br>beta-catenin localization, proliferation (Ki-67), apoptosis (TUNEL and M30<br /><br>assay) and tumor differentation.</p><br>