Transanal Endoscopic Microsurgery (TEM) After Radiochemotherapy for Rectal Cancer (CARTS)

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: NCT01273051
Recruitment Status : Completed
First Posted : January 10, 2011
Last Update Posted : April 14, 2017
Information provided by (Responsible Party):
Radboud University

Brief Summary:

In the Netherlands approximately 2300 new patients are diagnosed with rectal cancer each year. Standard treatment for patients with a T2 or T3 rectal cancer consists of preoperative short course of radiotherapy followed by surgery. In advanced cases long course of radiotherapy combined with chemotherapy is used instead of a short cause. In some of these advanced cases a complete remission is observed after a long course of radio-/chemotherapy. Patients who respond well to neo-adjuvant treatment carry a better prognosis.

Objective of this research is to evaluate whether neo-adjuvant chemo-/radiotherapy in small non-advanced rectal cancers can be used to obtain a complete or near complete remission. In these patients could a complete resection of the rectum as an organ be avoided by treating them with a local excision with the TEM-technique (Transanal Endoscopic Microsurgery) of the scar. The advantage for these patients is, that they do not need major abdominal surgery and in a substantial number of these patients the rectum can be preserved with a better function of continence.

Condition or disease Intervention/treatment Phase
Rectal Tumour Drug: Capecitabine Radiation: radiotherapy Procedure: TME resection Procedure: TEM surgery Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : November 2010
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Intervention Details:
    Drug: Capecitabine
    Capecitabine will be administered at a dose of 825 mg/m2 bid during radiotherapy treatment
    Radiation: radiotherapy
    radiation 25x2 Gy
    Procedure: TME resection
    All patients undergo a MRI of the pelvis and a rectoscopy and endorectal ultrasound 6 weeks after chemo radiation. Patients who do not respond or clinically have a T3 tumour either on visual measurements or post therapy MRI or endoanal ultrasound will be operated on with a TME resection 8 - 10 weeks after the last chemo radiation treatment.
    Procedure: TEM surgery

    All patients undergo a MRI of the pelvis and a rectoscopy and endorectal ultrasound 6 weeks after chemo radiation.Patients with a significant downsizing of the tumour (T0-T2) will be operated on by TEM surgery 8 -10 weeks after the last chemo radiation treatment.

    After TEM surgery, pathological assessment will dictate further treatment. Conservative treatment with careful follow-up will be performed in patients with a complete resection of a ypT0-1 rectal tumour. Patients with lymphangio invasion, an incomplete resected ypT1 (<2 mm margin), an ypT2 or ypT3 tumour after TEM will subsequently undergo TME surgery to remove the rectum within 4 weeks.

Primary Outcome Measures :
  1. Response [ Time Frame: Baseline and 6 weeks after chemoradiation therapy ]
    the response of the rectal carcinoma to chemo-/radiotherapy defined as complete response (no visible disease); partial response (more than 50% reduction of the tumour mass); no response (meaning an increase of the tumour mass less than 25% or a decrease of the tumour mass less than 50%); or progressive disease when the tumour mass increase more than 25% of the original tumour mass.

Secondary Outcome Measures :
  1. Quality of life [ Time Frame: baseline, 6-12-24 and 35 months after surgery ]
    Quality of life form EORTC-QLQC30 and 38. Determine the faecal continence and QOL after treatment with TEM surgery will be compared with TME treated patients.

  2. Local Recurrence [ Time Frame: 36 months, 60 months after surgery last enrolled patient ]
    Careful follow-up will determine the local recurrence rate of patients treated with TEM and TME surgery. This will be standard colorectal cancer follow-up with additional endo-anal endography and MRI for patients treated with TEM surgery during the first two years.

  3. Toxicity [ Time Frame: 4 weeks after surgery last enrolled patient ]

    Regional and systemic Toxicity/Side effects will be recorded according to the CTC-Toxicity Grading system, CTC-NCIC Toxicity Criteria v. 3.0. (See appendix to the protocol).

    Surgical and postoperative complications will be collected and assessed during interim analysis.

  4. Number of positive lymph nodes in patient who have been treated with classical surgery [ Time Frame: 4 weeks after surgery last enrolled patient ]
    The number of patients with positive lymph nodes after chemo radiation is expected to be less than 20%, this will carefully be monitored.

  5. The number of sphincter saving procedures [ Time Frame: 4 weeks after surgery last enrolled patient ]
    after organ sparing surgery by classical TEM or after TME surgery:

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

Inclusion Criteria:

  • Patients (aged >18 years) with histological proven adenocarcinoma of the distal part of the rectum (below 10 cm) without signs of distant metastases.
  • T1-3 tumour without lymph nodes > 5 mm at CT, MRI and endoanal ultrasound.
  • ANC > 1.5 x 109/l.
  • Thrombocytes > 100 x 109/l.
  • Creatinin clearance >50ml/min (according to the Cockcroft-Gault formula)
  • Total serum bilirubin < 24 mol/l or below <1.5 times the upper limit of the normal.
  • ASAT,ALAT: up to 5 times the upper limit.
  • Colonoscopy, colonography or virtual colonoscopy should exclude synchronous colorectal lesions in other parts of the colon.
  • ECOG performance score 0-2.
  • Fertile women should have adequate birth control during treatment.
  • Mental/physical/geographical ability to undergo treatment and follow-up.
  • Written informed consent (Dutch language).

Exclusion Criteria:

  • Patients with Grade 1-2 T1 tumors (can be treated with TEM surgery without chemoradiation therapy)
  • Patients with circular rectal tumor or tumors who are by other means unacceptable for TEM surgery (e.g. intra anal tumors).
  • Patients with faecal incontinence prior to the diagnosis of rectal cancer (complaints of soiling due to the tumor will not be an exclusion criterium).
  • Severe uncontrollable medical or neurological disease.
  • Patients with secondary prognosis determining malignancies.
  • Patients who have been treated with radiotherapy on the pelvis.
  • Use of Vitamin K antagonists.
  • Fenytoine and Allopurinol use.
  • Known DPD deficiency
  • Uncontrolled active infection, compromised immune status, psychosis, or CNS disease.
  • Pregnant or lactating women.
  • Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤ 6 months prior to randomisation), myocardial infarction (≤ 6 months prior to randomisation), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
  • Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of Capecitabine or patients at high risk for treatment complications. History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy).

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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): NCT01273051

University Medical Centre Nijmegen
Nijmegen, Gelderland, Netherlands, 6500 HB
Academisch Medisch Centrum
Amsterdam, Netherlands
Amsterdam, Netherlands
Slotervaart Ziekenhuis
Amsterdam, Netherlands
Amphia Ziekenhuis
Breda, Netherlands
IJsselland Ziekenhuis
Capelle aan de IJssel, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands, 5602 ZA
Leiden, Netherlands
Maastricht, Netherlands
Laurentius Ziekenhuis
Roermond, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
Instituut Verbeeten
Tilburg, Netherlands, 5042 SB
Utrecht, Netherlands
Sponsors and Collaborators
Radboud University
Principal Investigator: J.H.W de Wilt, Md PhD University Medical Centre Nijmegen

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Radboud University Identifier: NCT01273051     History of Changes
Other Study ID Numbers: CMO 2010_121
First Posted: January 10, 2011    Key Record Dates
Last Update Posted: April 14, 2017
Last Verified: April 2017

Keywords provided by Radboud University:
Rectal Cancer
Organ preservation

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents