Study of Micrometastases in Patients With Stage I or Stage II Localized Colon Cancer That Can Be Removed by Surgery
Recruitment status was: Recruiting
RATIONALE: Diagnostic procedures such as sentinel lymph node mapping may help doctors find patients who are at risk of developing micrometastases and plan better treatment.
PURPOSE: This randomized phase II/III trial is studying micrometastases in patients with stage I or stage II localized colon cancer that can be removed by surgery.
Other: active surveillance
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: lymph node mapping
Procedure: sentinel lymph node biopsy
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||The Influence of Micrometastases on Prognosis and Survival in Stage I-II Colon Cancer Patients: The EnRoute+ Study|
- Accrual rate (total number of pN0 patients included in the registration study monthly/center) (stage 1)
- Rate of upstaging in pN0 colon cancer patients (stage 1)
- Disease-free survival (DFS) at 3 years (stage 2)
- Percentage of successful sentinel lymph node mapping procedures using multivariate analysis (stage 2)
- Overall survival (OS) at 3 years (stage 2)
- Stratified analysis of DFS and OS according to total harvested lymph nodes per resected specimen and chemotherapy regimen (capecitabine and oxaliplatin versus capecitabine alone) (stage 2)
|Study Start Date:||July 2010|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
- To determine the subset of patients with stage I or II localized, resectable colon cancer (pN0) at risk for developing systemic metastases.
- To determine the clinical and prognostic relevance of occult nodal isolated tumor cells and micrometastases in these patients.
- To determine the benefits of adjuvant chemotherapy in patients with pN0micro+ colon cancer.
OUTLINE: This is a phase II feasibility study (stage 1) followed by a phase III multicenter, open-label, randomized, and controlled study (stage 2).
- Stage 1 (phase II feasibility study) After undergoing planned curative resection followed by ex vivo sentinel lymph node mapping (SLNM). Resected samples are examined. The sentinel lymph nodes of those deemed pN0 disease (no macroscopic metastases or angioinvasion) are further evaluated for micrometastases by serial sectioning and immunohistochemistry using pan-cytokeratin. pN0micro+ disease are defined as isolated tumor cells (ITC) < 0.2 mm or micrometastasis 0.2 - 2 mm. Patients with pN0 disease are followed-up once every 6 months for 3 years and then annually for 2 years.
stage 2 (phase III randomized study): Patients undergo planned surgery and ex vivo SLNM as in stage 1. Patients with pN0micro- disease are assigned to arm C; patients with pN0micro+ disease are randomized to 1 of 2 intervention arms (arms A and B). .
- Arm A (pN0micro+): Patients receive oral capecitabine twice daily on days 1-14 and oxaliplatin IV over 2 hours on day 1 OR oral capecitabine twice daily on days 1-14 alone according to standard protocol. Treatment repeats every 4 weeks for up to 8 courses. Patients are followed-up once every 6 months for 3 years and then annually for 2 years.
- Arm B (pN0micro+): Patients are followed-up once every 6 months for 3 years and then annually for 2 years.
- Arm C (pN0micro-): Patients are followed-up once every 6 months for 3 years and then annually for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01097265
|Jeroen Bosch Ziekenhuis|
|'s-Hertogenbosch, Netherlands, 5211 NL|
|Vrije Universiteit Medisch Centrum|
|Amsterdam, Netherlands, 1007 MB|
|Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital|
|Amsterdam, Netherlands, 1066 BE|
|Academisch Medisch Centrum at University of Amsterdam|
|Amsterdam, Netherlands, 1105 AZ|
|Eindhoven, Netherlands, 5602 ZA|
|University Medical Center Groningen|
|Groningen, Netherlands, 9700 RB|
|Leiden University Medical Center|
|Leiden, Netherlands, 2300 RC|
|Academisch Ziekenhuis Maastricht|
|Maastricht, Netherlands, 6202 AZ|
|Universitair Medisch Centrum St. Radboud - Nijmegen|
|Nijmegen, Netherlands, NL-6500 HB|
|University Medical Center Rotterdam at Erasmus Medical Center|
|Rotterdam, Netherlands, 3000 CA|
|University Medical Center Utrecht|
|Utrecht, Netherlands, 3584 CX|
|Principal Investigator:||Koop Bosscha, MD||Jeroen Bosch Ziekenhuis|