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

Primary Purpose

Rectal Tumour

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Capecitabine
radiotherapy
TME resection
TEM surgery
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Tumour focused on measuring Rectal Cancer, Radiochemotherapy, TEM, Organ preservation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • University Medical Centre Nijmegen
  • Academisch Medisch Centrum
  • NKI AVL
  • Slotervaart Ziekenhuis
  • Amphia Ziekenhuis
  • IJsselland Ziekenhuis
  • Catharina Ziekenhuis
  • LUMC
  • MAASTRO Clinic
  • Laurentius Ziekenhuis
  • Erasmus Medical Center
  • Instituut Verbeeten
  • Diakonessenhuis

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
The number of sphincter saving procedures
after organ sparing surgery by classical TEM or after TME surgery:

Full Information

First Posted
November 22, 2010
Last Updated
April 13, 2017
Sponsor
Radboud University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01273051
Brief Title
Transanal Endoscopic Microsurgery (TEM) After Radiochemotherapy for Rectal Cancer
Acronym
CARTS
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Tumour
Keywords
Rectal Cancer, Radiochemotherapy, TEM, Organ preservation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine will be administered at a dose of 825 mg/m2 bid during radiotherapy treatment
Intervention Type
Radiation
Intervention Name(s)
radiotherapy
Intervention Description
radiation 25x2 Gy
Intervention Type
Procedure
Intervention Name(s)
TME resection
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
TEM surgery
Intervention Description
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 Measure Information:
Title
Response
Description
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.
Time Frame
Baseline and 6 weeks after chemoradiation therapy
Secondary Outcome Measure Information:
Title
Quality of life
Description
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.
Time Frame
baseline, 6-12-24 and 35 months after surgery
Title
Local Recurrence
Description
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.
Time Frame
36 months, 60 months after surgery last enrolled patient
Title
Toxicity
Description
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.
Time Frame
4 weeks after surgery last enrolled patient
Title
Number of positive lymph nodes in patient who have been treated with classical surgery
Description
The number of patients with positive lymph nodes after chemo radiation is expected to be less than 20%, this will carefully be monitored.
Time Frame
4 weeks after surgery last enrolled patient
Title
The number of sphincter saving procedures
Description
after organ sparing surgery by classical TEM or after TME surgery:
Time Frame
4 weeks after surgery last enrolled patient

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J.H.W de Wilt, Md PhD
Organizational Affiliation
University Medical Centre Nijmegen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Centre Nijmegen
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6500 HB
Country
Netherlands
Facility Name
Academisch Medisch Centrum
City
Amsterdam
Country
Netherlands
Facility Name
NKI AVL
City
Amsterdam
Country
Netherlands
Facility Name
Slotervaart Ziekenhuis
City
Amsterdam
Country
Netherlands
Facility Name
Amphia Ziekenhuis
City
Breda
Country
Netherlands
Facility Name
IJsselland Ziekenhuis
City
Capelle aan de IJssel
Country
Netherlands
Facility Name
Catharina Ziekenhuis
City
Eindhoven
ZIP/Postal Code
5602 ZA
Country
Netherlands
Facility Name
LUMC
City
Leiden
Country
Netherlands
Facility Name
MAASTRO Clinic
City
Maastricht
Country
Netherlands
Facility Name
Laurentius Ziekenhuis
City
Roermond
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Facility Name
Instituut Verbeeten
City
Tilburg
ZIP/Postal Code
5042 SB
Country
Netherlands
Facility Name
Diakonessenhuis
City
Utrecht
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
22171697
Citation
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.
Results Reference
derived

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Transanal Endoscopic Microsurgery (TEM) After Radiochemotherapy for Rectal Cancer

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