This study has been transitioned to CTIS with ID 2024-517410-15-01 check the CTIS register for the current data. The aim of this study is to determine the oncological safety, treatment related morbidity, and the functional outcome of local excision…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of the study is local recurrence after 3 year follow-up.
Secondary outcome
Secondary mortality, morbidity, stoma rate, long term interventions, functional
outcomes, health related quality of life (HRQoL) and
costs.
Background summary
Colorectal cancer is the third most common cancer and second cause of cancer
related death in the Netherlands with 13,500 new cases each year. Due to the
introduction of the bowel cancer screening a shift is expected towards more
early cancers being detected. 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 It thereby enables the prediction of 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 tumor characteristics the TESAR trial is
designed.
Study objective
This study has been transitioned to CTIS with ID 2024-517410-15-01 check the CTIS register for the current data.
The aim of this study is to determine the oncological safety, treatment related
morbidity, and the functional outcome of local excision followed by adjuvant
chemo-radiotherapy compared to local excision followed by completion radical
resection of intermediate risk early rectal cancer.
Study design
In this international multicentre, partially randomised patient preference
trial, patients with complete excision of intermediate risk T1-2 rectal cancer
by transanal endoscopic surgery (TEM/TAMIS) or endoscopic excision (snare
polypectomy/EMR/ESD/Endoscopic intramuscular dissection(EID)) will be
randomised between organ preserving adjuvant chemoradiotherapy or completion
TME surgery. If patients are unwilling to be randomised, they will have the
option to choose between completion surgery and adjuvant chemoradiotherapy.
Patients who decline further treatment after local excision will be invited to
join the registration cohort.
Intervention
The study treatment consists of adjuvant chemo-radiotherapy (25x1.8 Gy) limited
to the mesorectum with concurrent capecitabine (825 mg/m2). To monitor the risk
of recurrence, there will be additional follow up with frequent MRI and
endoscopy in the experimental arm. For a period of 5 weeks patients will
receive the treatment, only during weekdays.
Study burden and risks
The study compares two accepted treatment strategies for rectal carcinoma,
aiming to demonstrate reduced treatment-related morbidity in the intervention
group. The intervention arm involves an existing treatment for rectal carcinoma
with relatively low morbidity. Patients in the intervention group will undergo
a 5-week course of radiation therapy, which may impose some burden on them. Any
risks associated with chemoradiation, such as enteritis, diarrhea, mild
neurotoxicity, and impaired wound healing, will be closely monitored and
documented using the comprehensive complication index and the NCI toxicity
score. In contrast, the control group will undergo a major radical resection
procedure, accompanied by associated hospitalizations, morbidity, and
mortality.
de Boelelaan 1118
Amsterdam 1081 HV
NL
de Boelelaan 1118
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
1. Patient has had an endoluminal local excision (by TEM, TAMIS, TSPM,
EMR/ESD/endoscopic intramuscular dissection or polypectomy) of an early rectal
cancer without carcinoma in the resection plane.
2. Patients without carcinoma in the resection plane or in case of unreliable
resection planes (EMR/ESD) no macroscopic residual tumour confirmed by
endoscopy are eligible for randomisation.
3. Only lesions for which TME surgery is indicated can be included (If a
partial mesorectal excision (PME) is indicated the patient should be excluded).
4. Pathological confirmation of the rectal adenocarcinoma fulfilling the
following criteria: T1 with size 3-5 cm of carcinoma or pT1, maximum size of
carcinoma of 3 cm, with at least poor differentiation, Haggit 4 and/or sm3,
tumour budding, lymphatic and/or venous invasion.
5. Pathological confirmation of the rectal adenocarcinoma fulfilling the
following criteria: pT2, maximum size of carcinoma of 3 cm, well/moderate
differentiated and without tumour budding or lymphatic or venous invasion.
6. Complete colonoscopy, without synchronous colorectal cancer
7. cN0 stage based on pelvic MRI; lymph nodes smaller than 10 mm will be
considered as benign, independent of morphologic features. Staging done within
6 weeks before randomisation.
8. Adequate distant staging (X-thorax or CT-thorax and CT-abdomen) without
signs of distant metastasis (cM0)
9. Male or female, Age > 18 years.
10. Life expectancy of at least 12 months.
11. Medically fit (WHO 0-2) to undergo radical surgery and/or radiation.
12. No contraindications to chemotherapy, including adequate blood counts;
- white blood count >= 4.0 x 10 9/l
- platelet count >=100 x 109/l
- clinical acceptable haemoglobin levels
- bilirubin < 35 umol/l
- creatinine levels indicating renal clearance of >=50 ml/min
13. The patient is willing and able to comply with the protocol for the
duration of the study, and scheduled follow-up visits and examinations.
14. Written (signed and dated) informed consent and be capable of co-operating
with protocol.
Exclusion criteria
1. Incomplete or inconclusive resection margin with macroscopic residual tumour.
2. T1 tumour with carcinoma < 3 cm, moderate/well differentiated, without
sm3/Haggit 4,tumour budding, 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 that interferes with the outcomes 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-517410-15-01 |
| EudraCT | EUCTR2015-000689-79-NL |
| CCMO | NL50364.029.15 |