Rectal Preserving Treatment for Early Rectal Cancer. A Multi-centred Randomised Trial of Radical Surgery Versus Adjuvant Chemoradiotherapy After Local Excision for Early Rectal Cancers

Phase 3

• Conditions: Rectal Cancer
• Interventions: Procedure: Additional TME surgery; Radiation: Adjuvant chemoradiotherapy; Drug: capecitabine

• Registration Number: NCT02371304
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

Current therapy for early colorectal cancer is radical Total Mesorectal Excision (TME). Colorectal surgical resections are accompanied with high morbidity of up to 33% and 90 days mortality of up to 9% in the fragile elderly patients as is seen in the results of the Dutch Surgical Colorectal Audit (DSCA) of 2013. Additionally, rectal cancer surgery is associated with substantial loss of health related quality of life due to defecation disorders, incontinence, sexual dysfunction and stoma related morbidity. These disadvantages are acceptable when radical surgery is the only option for cure. Advances in technology enabled the development of local excision of early rectal cancer with precise endoluminal microsurgery or local endoscopic excision resulting in a significant decrease in short- and long term morbidity. However current evidence is of inadequate quality to conclude on the oncologic safety of local treatment for early rectal cancer. Imaging can predict outcome and tailors treatment in more advanced cancer but fails in early cancer. Pathological assessment of the excised tumor tissue provides the optimal information on tumor stage, tumor characteristics and tumor differentiation, thereby it enables to predict the risk of recurrence after local treatment alone. For early rectal cancers, with a low risk on recurrence based on favourable tumor characteristics local excision is seen as safe and these patients do not require an additional treatment. However, for patients with early rectal cancer with a higher risk on recurrence based on tumor characteristics there is no consensus on the additional treatment after local excision. According to the National guideline these patients receive a TME procedure. However, for this subgroup of patients local treatment followed by chemoradiotherapy might also be oncological safe. Current evidence is of inadequate quality to be conclusive. For this subgroup of patients with early rectal cancer with high risk tumorcharacteristics the TESAR trial is designed, in which patiens will be randomised after local endoluminal excision between an additional TME-procedure (standard) and adjuvant chemoradiotherapy. Primary endpoint of the study will be local recurrence at 3 three year follow-up.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-02-18
• Study First Submitted QC: 2015-02-24
• Study First Posted: 2015-02-25
• Study Start: 2015-10
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-20
• Last Update Posted: 2020-05-21
• Primary Completion: 2022-06
• Study Completion: 2023-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 302

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Incomplete or inconclusive resection margin with macroscopic residual tumour.
2. T1 tumour with carcinoma < 3 cm, moderate/well differentiated, without sm3, venous or lymphatic invasion.
3. T1 tumour with carcinoma of >5 cm and T2 tumour with carcinoma of > 3 cm.
4. Presence of metastatic disease or recurrent rectal tumour.
5. Previous pelvic radiation.
6. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
7. Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.
8. Pregnancy, breast-feeding or fertile women without active birth control.
9. Clinically significant (i.e. active) cardiovascular disease for example cerebro vascular accidents (<6 months prior to randomization), myocardial infarction (<6 months prior to randomization), unstable angina, New York Heart Association (NYHA) grade II or higher, congestive heart failure, serious cardiac arrhythmia requiring medication.
10. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
11. History of severe and unexpected reactions to fluoropyrimidine therapy.
12. Hypersensitivity to capecitabine.
13. Patients with severe hepatic impairment.
14. Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
15. Patients known with dihydropyrimidine dehydrogenase deficiency
16. Any contra-indications to undergo MRI imaging.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Total Mesorectal Excision	Additional TME surgery	After local excision patients will receive additional TME surgery
Adjuvant chemoradiotherapy	capecitabine	After local excision. Patients will receive capecitabine 825 mg/m2 twice a day for 5 weeks only on weekdays. This will be combined with 1.8 Gy in 25 fractions with a limited dose only on the mesorectum
Adjuvant chemoradiotherapy	Adjuvant chemoradiotherapy	After local excision. Patients will receive capecitabine 825 mg/m2 twice a day for 5 weeks only on weekdays. This will be combined with 1.8 Gy in 25 fractions with a limited dose only on the mesorectum

Primary Outcome Measures

Name	Time	Method
Recurrence free at 3 year follow-up	3 year

Secondary Outcome Measures

Name	Time	Method
Treatment related morbidity	1,3 and 5 year follow-up

Trial Locations

Locations (1)

VU University Medical Center; 🇳🇱 Amsterdam, Netherlands