Transanal Endoscopic Microsurgery (TEM) After Radiochemotherapy for Rectal Cancer

NCT01273051 | Completed Phase 2 DMC

• 1 other identifier: CMO 2010_121
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 13

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.

Conditions

Rectal Tumour

Keywords

Rectal Cancer; Radiochemotherapy; TEM; Organ preservation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Quality of life

  baseline, 6-12-24 and 35 months after surgery

• Local Recurrence

  36 months, 60 months after surgery last enrolled patient

• Toxicity

  4 weeks after surgery last enrolled patient

• Number of positive lymph nodes in patient who have been treated with classical surgery

  4 weeks after surgery last enrolled patient

• The number of sphincter saving procedures

  4 weeks after surgery last enrolled patient

Interventions

Capecitabine DRUG

Capecitabine will be administered at a dose of 825 mg/m2 bid during radiotherapy treatment

radiotherapy RADIATION

radiation 25x2 Gy

TME resection PROCEDURE

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.

TEM surgery PROCEDURE

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (13)

University Medical Centre Nijmegen

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Academisch Medisch Centrum

Amsterdam, Netherlands

Location

NKI AVL

Amsterdam, Netherlands

Location

Slotervaart Ziekenhuis

Amsterdam, Netherlands

Location

Amphia Ziekenhuis

Breda, Netherlands

Location

IJsselland Ziekenhuis

Capelle aan den IJssel, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, 5602 ZA, Netherlands

Location

LUMC

Leiden, Netherlands

Location

MAASTRO Clinic

Maastricht, Netherlands

Location

Laurentius Ziekenhuis

Roermond, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Instituut Verbeeten

Tilburg, 5042 SB, Netherlands

Location

Diakonessenhuis

Utrecht, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 22171697 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• J.H.W de Wilt, Md PhD

  University Medical Centre Nijmegen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: January 10, 2011
• Study Start: November 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2015
• Last Updated: April 14, 2017

Record last verified: 2017-04

Locations

NL (13)