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

CHEMORADIOTHERAPY FOR RECTAL CANCER IN THE DISTAL RECTUM FOLLOWED BY ORGANSPARING TRANSANAL ENDOSCOPIC MICROSURGERY: CARTS Study CApecitabine, Radiotherapy and Tem Surgery. A PHASE II, FEASIBILITY TRIAL

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.

Study Overview

• Status: Completed
• Conditions: Rectal Tumour
• Intervention / Treatment: Drug: Capecitabine; Radiation: radiotherapy; Procedure: TME resection; Procedure: TEM surgery

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum
  • Amsterdam, Netherlands
    • Slotervaart Ziekenhuis
  • Amsterdam, Netherlands
    • NKI AVL
  • Breda, Netherlands
    • Amphia Ziekenhuis
  • Capelle aan de IJssel, Netherlands
    • IJsselland ziekenhuis
  • Eindhoven, Netherlands, 5602 ZA
    • Catharina Ziekenhuis
  • Leiden, Netherlands
    • LUMC
  • Maastricht, Netherlands
    • Maastro clinic
  • Roermond, Netherlands
    • Laurentius Ziekenhuis
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Tilburg, Netherlands, 5042 SB
    • Instituut Verbeeten
  • Utrecht, Netherlands
    • Diakonessenhuis
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • University Medical Centre Nijmegen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	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.	Baseline and 6 weeks after chemoradiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	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.	baseline, 6-12-24 and 35 months after surgery
Local Recurrence	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.	36 months, 60 months after surgery last enrolled patient
Toxicity	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 weeks after surgery last enrolled patient
Number of positive lymph nodes in patient who have been treated with classical surgery	The number of patients with positive lymph nodes after chemo radiation is expected to be less than 20%, this will carefully be monitored.	4 weeks after surgery last enrolled patient
The number of sphincter saving procedures	after organ sparing surgery by classical TEM or after TME surgery:	4 weeks after surgery last enrolled patient

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: J.H.W de Wilt, Md PhD, University Medical Centre Nijmegen

Publications and helpful links

General Publications

• Bokkerink GM, de Graaf EJ, Punt CJ, Nagtegaal ID, Rutten H, Nuyttens JJ, van Meerten E, Doornebosch PG, Tanis PJ, Derksen EJ, Dwarkasing RS, Marijnen CA, Cats A, Tollenaar RA, de Hingh IH, Rutten HJ, van der Schelling GP, Ten Tije AJ, Leijtens JW, Lammering G, Beets GL, Aufenacker TJ, Pronk A, Manusama ER, Hoff C, Bremers AJ, Verhoef C, de Wilt JH. The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery. BMC Surg. 2011 Dec 15;11:34. doi: 10.1186/1471-2482-11-34.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: November 22, 2010
• First Submitted That Met QC Criteria: January 7, 2011
• First Posted (Estimate): January 10, 2011

Study Record Updates

• Last Update Posted (Actual): April 14, 2017
• Last Update Submitted That Met QC Criteria: April 13, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Rectal Cancer; Organ preservation; Radiochemotherapy; TEM
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: CMO 2010_121