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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2011 by National Cancer Institute (NCI)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01097265
First received: March 31, 2010
Last updated: August 9, 2013
Last verified: September 2011
  Purpose

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 Intervention 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

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Accrual rate (total number of pN0 patients included in the registration study monthly/center) (stage 1) [ Designated as safety issue: No ]
  • Rate of upstaging in pN0 colon cancer patients (stage 1) [ Designated as safety issue: No ]
  • Disease-free survival (DFS) at 3 years (stage 2) [ Designated as safety issue: No ]
  • Percentage of successful sentinel lymph node mapping procedures using multivariate analysis (stage 2) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (OS) at 3 years (stage 2) [ Designated as safety issue: No ]
  • 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) [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: July 2010
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • 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.
  • .
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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)

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01097265

Locations
Netherlands
Jeroen Bosch Ziekenhuis Recruiting
's-Hertogenbosch, Netherlands, 5211 NL
Contact: Contact Person    31-73-699-2701    k.bosscha@jbz.nl   
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      
Vrije Universiteit Medisch Centrum Recruiting
Amsterdam, Netherlands, 1007 MB
Contact: Contact Person    31-20-444-4300      
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    c.j.h.van_de_velde@lumc.nl   
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    c.punt@onco.umcn.nl   
University Medical Center Rotterdam at Erasmus Medical Center Recruiting
Rotterdam, Netherlands, 3000 CA
Contact: Contact Person    31-10-463-5995    w.r.schouten@erasmusmc.nl   
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Contact Person    31-30-250-9111      
Sponsors and Collaborators
Jeroen Bosch Ziekenhuis
Investigators
Principal Investigator: Koop Bosscha, MD Jeroen Bosch Ziekenhuis
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01097265     History of Changes
Other Study ID Numbers: JBZ-EnRoute+, CDR0000668525, EUDRACT-2010-018612-32, EU-21016
Study First Received: March 31, 2010
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I colon cancer
stage II colon cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Micrometastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Neoplasm Metastasis
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014