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Study of Micrometastases in Patients With Stage I or Stage II Localized Colon Cancer That Can Be Removed by Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01097265
Recruitment Status : Unknown
Verified September 2011 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
First Posted : April 1, 2010
Last Update Posted : August 12, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: capecitabine Drug: oxaliplatin Other: active surveillance Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: lymph node mapping Procedure: sentinel lymph node biopsy Phase 2 Phase 3

Detailed Description:


  • 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.
  • .

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Masking: None (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
Study Start Date : July 2010
Estimated Primary Completion Date : January 2015

Primary Outcome Measures :
  1. Accrual rate (total number of pN0 patients included in the registration study monthly/center) (stage 1)
  2. Rate of upstaging in pN0 colon cancer patients (stage 1)
  3. Disease-free survival (DFS) at 3 years (stage 2)
  4. Percentage of successful sentinel lymph node mapping procedures using multivariate analysis (stage 2)

Secondary Outcome Measures :
  1. Overall survival (OS) at 3 years (stage 2)
  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)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or radiologically confirmed primary colon cancer

    • Stage I or II disease
  • Clinically localized disease judged potentially resectable for cure, without intraoperatively gross nodal involvement
  • Planning to undergo elective resection of the tumor
  • No histologically or radiologically confirmed locoregional lymph node or distant metastasis
  • No disseminated disease
  • No clinical tumor perforation or obstruction
  • Patients enrolled in stage 2 and undergoing randomization must also meet the following criteria:

    • pN0micro+ disease as evidenced by detection of sentinel lymph node isolated tumor cells (<0.2 mm) or micrometastasis (0.2 - 2 mm)
    • No high-risk pN0 disease meeting any of the following criteria:

      • Less then 10 lymph nodes detected in resected specimen
      • Invasion in other organs (T4, Nx, Mx)
      • Colon perforation at presentation
      • Obstruction at presentation
      • Angioinvasion at pathological examination
    • No rectal cancer
    • No clinically positive nodal tumors or advanced disease (stage III or Dukes stage C disease)


  • Patients enrolled in stage 2 and undergoing randomization must also meet the following criteria:

    • WHO performance status 0-1 or American Society of Anesthesiologists Physical Status classification 1-2
    • Not pregnant or nursing
    • Able to comply with requirements of the study
    • Must be fit to undergo chemotherapy treatment
    • No other current serious illness or medical conditions, including any of the following:

      • Severe cardiac illness (NYHA class III-IV disease)
      • Significant neurologic or psychiatric disorders
      • Uncontrolled infections
      • Active disseminated intravascular coagulation
      • Other serious underlying medical conditions that could impair the ability of the patient to participate in the study
    • No known hypersensitivity to study drugs
    • No definite contraindications for the use of corticosteroids


  • No prior colorectal surgery
  • Patients enrolled in stage 2 and undergoing randomization must also meet the following criteria:

    • No prior chemotherapy (for patients enrolled in stage 2 and undergoing randomization only)
    • At least 4 weeks since prior and no other concurrent experimental drugs
    • No concurrent immunosuppressive or antiviral drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01097265

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Jeroen Bosch Ziekenhuis Recruiting
's-Hertogenbosch, Netherlands, 5211 NL
Contact: Contact Person    31-73-699-2701   
Vrije Universiteit Medisch Centrum Recruiting
Amsterdam, Netherlands, 1007 MB
Contact: Contact Person    31-20-444-4300      
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital Recruiting
Amsterdam, Netherlands, 1066 BE
Contact: Contact Person    31-20-512-9111      
Academisch Medisch Centrum at University of Amsterdam Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Contact Person    31-20-566-9111      
Catharina Ziekenhuis Recruiting
Eindhoven, Netherlands, 5602 ZA
Contact: Contact Person    31-40-239-9111      
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9700 RB
Contact: Contact Person    31-50-361-2317      
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2300 RC
Contact: Contact Person    31-71-526-2309   
Academisch Ziekenhuis Maastricht Recruiting
Maastricht, Netherlands, 6202 AZ
Contact: Contact Person    31-43-387-7025      
Universitair Medisch Centrum St. Radboud - Nijmegen Recruiting
Nijmegen, Netherlands, NL-6500 HB
Contact: Contact Person    31-24-361-0353   
University Medical Center Rotterdam at Erasmus Medical Center Recruiting
Rotterdam, Netherlands, 3000 CA
Contact: Contact Person    31-10-463-5995   
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Contact Person    31-30-250-9111      
Sponsors and Collaborators
Jeroen Bosch Ziekenhuis
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Principal Investigator: Koop Bosscha, MD Jeroen Bosch Ziekenhuis
Publications of Results:
Layout table for additonal information Identifier: NCT01097265    
Other Study ID Numbers: JBZ-EnRoute+
CDR0000668525 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: April 1, 2010    Key Record Dates
Last Update Posted: August 12, 2013
Last Verified: September 2011
Keywords provided by National Cancer Institute (NCI):
stage I colon cancer
stage II colon cancer
Additional relevant MeSH terms:
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Colonic Neoplasms
Neoplasm Micrometastasis
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents