Pre-operative Decitabine in Colon Cancer: a Proof of Principle Study

NCT01882660 | Terminated DMC

• 1 other identifier: NL44048.018.13
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  30 minutes after surgery

Secondary Outcomes (6)

• Wnt target methylation.

  30 minutes after surgery

• CIMP gene methylation

  30 minutes after surgery

• Beta-catenin localisation

  30 minutes after surgery

• Proliferation (Ki-67)

  30 minutes after surgery

• Apoptose (TNEL en M30 assay)

  30 minutes after surgery

Study Arms (1)

Decitabine treatment

EXPERIMENTAL

Treatment with decitabine

Drug: Decitabine

Interventions

Decitabine DRUG

Decitabine treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• In order to participate in the first part of the study, five extra fresh biopsies to determine tumor methylation status, a subject must meet all of the following criteria:
• 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.
• \. 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:
• Patients with biopsy proven colon cancer who will undergo primary tumor resection.
• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: May 24, 2013
• First Posted: June 20, 2013
• Study Start: July 1, 2013
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: December 19, 2022

Record last verified: 2022-12

Locations

NL (1)