E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
colon cancer |
Dikkedarm kanker |
|
E.1.1.1 | Medical condition in easily understood language |
colon cancer |
Dikkedarm kanker |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
Het bestuderen van de effecten van een eenmalige behandeling met Decitabine op Wnt target gen van dikkedarmkanker. |
|
E.2.2 | Secondary objectives of the trial |
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 |
Het bestuderen van de effecten van een eenmalige behandeling met Decitabine op CIMP gen methylatie en tumor differentiatie van dikkedarmkanker. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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:
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.
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 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. |
Patiënten met een (hoge verdenking op) dikkedarmkanker. |
|
E.4 | Principal exclusion criteria |
A potential subject for the first part of the study - extra biopsies to determine tumor methylation status - 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.
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. Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol. |
Psychologische of andere redenen waardoor informed consent en (veilige) deelname niet mogelijk is.
Overgevoeligheid voor decitabine.
Een andere behandeling van de tumor in de wachttijd tot de operatie. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Wnt target gene expression (APCDD1, AXIN2, DKK1, LGR5 and ASCL2). |
Wnt target gen expressie (APCDD1, AXIN2, DKK1, LGR5 and ASCL2) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After surgery of colon cancer |
Na operatie van de dikkedarmtumor |
|
E.5.2 | Secondary end point(s) |
Wnt target and CIMP gene methylation, -catenin localization, proliferation (Ki-67), apoptosis (TUNEL and M30 assay) and tumor differentation. |
Wnt target en CIMP gen methylatie, beta-catenin localisatie, proliferatie (Ki-67), apoptose (TUNEL en M30 assay) en tumor differentiatie |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After surgery of colon cancer |
Na operatie van de dikkedarmtumor |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |