Colorectal CancerPhase 2/3NCT01097265
Study of Micrometastases in Patients With Stage I or Stage II Localized Colon Cancer That Can Be Removed by Surgery
A Phase 2/3 study testing capecitabine, oxaliplatin and active surveillance in people with Colorectal Cancer, run by Jeroen Bosch Ziekenhuis at 11 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- capecitabine, oxaliplatin and active surveillance
- Type of treatment
- Surgery or procedure
- How many people
- 1,500 participants
- Where
- 11 sitesNetherlands
- Study dates
- Jul 2010to Jan 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Netherlands11 sites, 11 recruiting
- Recruiting
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5211 NL
Contact Person, 31-73-699-2701, k.bosscha@jbz.nl
- Recruiting
Vrije Universiteit Medisch Centrum
Amsterdam, 1007 MB
Contact Person, 31-20-444-4300
- Recruiting
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, 1066 BE
Contact Person, 31-20-512-9111
- Recruiting
Academisch Medisch Centrum at University of Amsterdam
Amsterdam, 1105 AZ
Contact Person, 31-20-566-9111
- Recruiting
Catharina Ziekenhuis
Eindhoven, 5602 ZA
Contact Person, 31-40-239-9111
- Recruiting
University Medical Center Groningen
Groningen, 9700 RB
Contact Person, 31-50-361-2317
- Recruiting
Leiden University Medical Center
Leiden, 2300 RC
Contact Person, 31-71-526-2309, c.j.h.van_de_velde@lumc.nl
- Recruiting
Academisch Ziekenhuis Maastricht
Maastricht, 6202 AZ
Contact Person, 31-43-387-7025
- Recruiting
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, NL-6500 HB
Contact Person, 31-24-361-0353, c.punt@onco.umcn.nl
- Recruiting
University Medical Center Rotterdam at Erasmus Medical Center
Rotterdam, 3000 CA
Contact Person, 31-10-463-5995, w.r.schouten@erasmusmc.nl
- Recruiting
University Medical Center Utrecht
Utrecht, 3584 CX
Contact Person, 31-30-250-9111
About this study
Official title: The Influence of Micrometastases on Prognosis and Survival in Stage I-II Colon Cancer Patients: The EnRoute+ Study
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.
Read the 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.
- .
- Conditions
- Colorectal Cancer
- Being tested
- capecitabine, oxaliplatin, active surveillance, laboratory biomarker analysis, adjuvant therapy
- Keywords
- stage I colon cancer, stage II colon cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capecitabineDrug
oxaliplatinDrug
active surveillanceOther
laboratory biomarker analysisOther
adjuvant therapyProcedure or surgery
lymph node mappingProcedure or surgery
sentinel lymph node biopsyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Secondary outcomes (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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2010 (estimated)
- Study startJul 2010
- Primary completionJan 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jeroen Bosch Ziekenhuis
- Sponsor type
- University, hospital or other
- Investigators
- Koop Bosscha, MD, Principal investigator, Jeroen Bosch Ziekenhuis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01097265
- Sponsor's protocol ID
- JBZ-EnRoute+
- Other IDs
- CDR0000668525, EUDRACT-2010-018612-32, EU-21016
- Status last verified
- Sep 2011
- First submitted
- 31 Mar 2010
- Last updated
- 12 Aug 2013
- Results posted
- No
Publications
Lips DJ, Koebrugge B, Liefers GJ, van de Linden JC, Smit VT, Pruijt HF, Putter H, van de Velde CJ, Bosscha K. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute plus sign in circle Study. BMC Surg. 2011 May 11;11:11. doi: 10.1186/1471-2482-11-11.
PubMed 21569373
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Micrometastases on Prognosis and Survival in Stage I-II Colon Cancer Patients: The EnRoute+ Study
- ClinicalTrials.gov ID
- NCT01097265
- Acronym / sponsor ID
- JBZ-EnRoute+
- Conditions
- Colorectal Cancer
- Keywords
- stage I colon cancer, stage II colon cancer
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Jeroen Bosch ZiekenhuisUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Jan 2015 (estimated)
- First posted
- 1 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
- .
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| capecitabine | Drug | – |
| oxaliplatin | Drug | – |
| active surveillance | Other | – |
| laboratory biomarker analysis | Other | – |
| adjuvant therapy | Procedure or surgery | – |
| lymph node mapping | Procedure or surgery | – |
| sentinel lymph node biopsy | Procedure or surgery | – |
Primary outcome
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)
2 secondary outcomes
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2013.
- Results publication: PubMed 21569373Lips DJ, Koebrugge B, Liefers GJ, van de Linden JC, Smit VT, Pruijt HF, Putter H, van de Velde CJ, Bosscha K. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute plus sign in circle Study. BMC Surg. 2011 May 11;11:11. doi: 10.1186/1471-2482-11-11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Koop Bosscha, MD principal investigator
Jeroen Bosch Ziekenhuis
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing capecitabine, oxaliplatin and active surveillance in people with Colorectal Cancer, run by Jeroen Bosch Ziekenhuis at 11 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accrual rate (total number of pN0 patients included in the registration study monthly/center) (stage 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01097265, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2013.