Clinical trial NCT01273051: Transanal Endoscopic Microsurgery (TEM) After Radiochemotherapy for Rectal Cancer
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectal Tumour
Keywords: Rectal Cancer
Radiochemotherapy
TEM
Organ preservation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2011-01-10
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Response
timeFrame: Baseline and 6 weeks after chemoradiation therapy
Secondary outcomes:
measure: Quality of life
timeFrame: baseline, 6-12-24 and 35 months after surgery
measure: Local Recurrence
timeFrame: 36 months, 60 months after surgery last enrolled patient
measure: Toxicity
timeFrame: 4 weeks after surgery last enrolled patient
measure: Number of positive lymph nodes in patient who have been treated with classical surgery
timeFrame: 4 weeks after surgery last enrolled patient
measure: The number of sphincter saving procedures
timeFrame: 4 weeks after surgery last enrolled patient
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: University Medical Centre Nijmegen
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Amsterdam
country: Netherlands
facility: NKI AVL
city: Amsterdam
country: Netherlands
facility: Slotervaart Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Capelle aan de IJssel
country: Netherlands
facility: IJsselland Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Leiden
country: Netherlands
facility: LUMC
city: Maastricht
country: Netherlands
facility: MAASTRO Clinic
city: Roermond
country: Netherlands
facility: Laurentius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Tilburg
country: Netherlands
facility: Instituut Verbeeten
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
Study officials:
affiliation: University Medical Centre Nijmegen
name: J.H.W de Wilt, Md PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.