Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01882660
Other study ID # NL44048.018.13
Secondary ID
Status Terminated
Phase N/A
First received
Last updated
Start date July 2013
Est. completion date January 2018

Study information

Verified date December 2022
Source Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 10
Est. completion date January 2018
Est. primary completion date January 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility In- and exclusion criteria first part: 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: Inclusion criteria: 1. Biopsy proven colon cancer or high suspicion of colon cancer on a previous endoscopy. 2. Planned endoscopy. 3. Age = 18yr. 4. ECOG/ WHO performance 0-2. 5. Written informed consent. Exclusion criteria: 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: Inclusion criteriä: 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 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. Exclusion criteria: 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Decitabine


Locations

Country Name City State
Netherlands Academic Medical Center Amsterdam

Sponsors (1)

Lead Sponsor Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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. 30 minutes after surgery
Secondary CIMP gene methylation See above 30 minutes after surgery
Secondary Beta-catenin localisation See above 30 minutes after surgery
Secondary Proliferation (Ki-67) See above 30 minutes after surgery
Secondary Apoptose (TNEL en M30 assay) See above. 30 minutes after surgery
Secondary Tumor differentiation See above 30 minutes after surgery
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05551052 - CRC Detection Reliable Assessment With Blood
Completed NCT03457454 - Reducing Rural Colon Cancer Disparities
Recruiting NCT06006390 - CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT04088955 - A Digimed Oncology PharmacoTherapy Registry
Recruiting NCT06010862 - Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors Phase 1
Terminated NCT01347645 - Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer Phase 1/Phase 2
Completed NCT03390907 - Hybrid APC Assisted EMR for Large Colon Polyps N/A
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Completed NCT04079478 - The AID Study: Artificial Intelligence for Colorectal Adenoma Detection
Active, not recruiting NCT04057274 - Acute Effect of modeRate-intensity aerOBIc Exercise on Colon Cancer Cell Growth N/A
Recruiting NCT03190941 - Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients Phase 1/Phase 2
Not yet recruiting NCT05147545 - Impact of Exercise and Hyperlipidic Meal on Free Circulating DNA in Patients With Metastatic Colonic Cancer and Healthy Subjects N/A
Recruiting NCT05026268 - The Laparoscopic Right Colectomy With Intracoroporeal Anastomosis N/A
Not yet recruiting NCT03277235 - Effect of a Resilience Model-Based Care Plan in Newly Diagnosed Colorectal Cancer Patients N/A
Active, not recruiting NCT02730702 - Colon Cancer Risk-stratification Via Optical Analysis of Rectal Ultrastructure
Active, not recruiting NCT02959541 - PK/PD Investigation of Calciumfolinat in Blood, Tumor and Adjacent Mucosa in Patient With Colon Cancer N/A
Completed NCT02810652 - Perioperative Geriatrics Intervention for Older Cancer Patients Undergoing Surgical Resection N/A
Recruiting NCT02577627 - Multi-Indication, Retrospective Oncological Study to Validate the Accuracy in Predicting TTP by PrediCare in Patients Under SOC N/A
Terminated NCT02628535 - Safety Study of MGD009 in B7-H3-expressing Tumors Phase 1
Recruiting NCT02526836 - Complete Mesocolic Excision With Central Vessel Ligation Compared With Conventional Surgery for Colon Cancer Phase 2/Phase 3