A multi-centred, partially randomised, patient-preference trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

14 Jan 2025 → ongoing

Decision date (initial)

2025-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

KWF Dutch Cancer Society

External identifiers

EU CT number

2024-517410-15-01

EudraCT number

2015-000689-79

ClinicalTrials.gov

NCT02371304

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The aim of this study is to determine oncological safety of rectal preserving therapy for intermediate-risk early rectal cancer by comparing completion surgery with adjuvant chemoradiotherapy and surveillance after local excision.

Secondary objectives 7

1. To compare organ preserving therapy with radical surgery in terms of treatment related morbidity.
2. To assess unsalvagable pelvic disease at three years, defined as locoregional recurrence that is not able to be treated with curative intent.
3. To determine three and five-year disease free survival and overall survival.
4. To determine stoma-free survival at one-, three- and five-years for both group of patients.
5. To evaluate the influence of organ preserving therapy on long-term morbidity.
6. To investigate the impact of organ preserving therapy on HRQol and functional outcomes compared to radical surgery.
7. Determining cost-effectiveness of organ preserving therapy.

Conditions and MedDRA coding

Rectal cancer

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. The patient has had an endoluminal local excision (by TEM, TAMIS, TSPM, EMR, ESD, endoscopic full thickness resection, endoscopic intramuscular dissection or polypectomy) of an early rectal cancer without carcinoma in the resection plane.
2. Patients with unreliable resection planes (EMR/ESD) are eligible for randomisation if no macroscopic residual tumour is found during endoscopy.
3. Patients with carcinoma in the resection plane are eligible for randomisation after re-excision that shows no carcinoma in the resection plane.
4. Only lesions for which TME surgery is indicated can be included (if a partial mesorectal excision (PME) is indicated the patient should be excluded).
5. 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.
6. Pathological confirmation of the rectal adenocarcinoma fulfilling the following criteria: pT2, maximum size of carcinoma of 3 cm, well/moderate differentiated and without lymphatic or venous invasion.
7. Complete colonoscopy, without synchronous colorectal cancer.
8. 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.
9. Adequate distant staging (X-thorax or CT-thorax and CT-abdomen) without signs of distant metastasis (cM0).
10. Male or female, age > 18 years.
11. Life expectancy of at least 12 months.
12. Medically fit (WHO 0-2) to undergo radical surgery and/or radiation.
13. 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
14. The patient is willing and able to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations.
15. Written (signed and dated) informed consent and be capable of co-operating with protocol.

Exclusion criteria 16

1. Incomplete or inconclusive resection margin with macroscopic residual tumour.
2. T1 tumour with carcinoma <3 cm, moderate/well differentiated, without sm3/Haggit4, 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 might influence study 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 cerebrovascular accidents (<6 months prior to randomisation), myocardial infarction (<6 months prior to randomisation), 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Three-year local recurrence rate

Secondary endpoints 7

1. Short-term morbidity: treatment related morbidity that occurs during treatment or within 30 days after the allocated treatment. The Comprehensive Classification index (see appendix) (36) and the NCI CTCAE Toxicity criteria will be used to assess to degree of morbidity in both separate treatment arms.
2. Unsalvagable pelvic disease at three years, defined as locoregional recurrence that is not able to be treated with curative intent.
3. Stoma rate at one, three and five year follow-up.
4. Long-term morbidity: long-term morbidity such as surgical re-interventions and readmissions related to the primary intervention will be evaluated at one, three and five years.
5. Functional outcome and HRQoL after therapy will be measured using the validated questionnaires EQ-5D, EORTC QLQ C29 & C30 and the LARS score for functional outcomes at admission and at 3, 6, 12, 24 and 36 months post-operatively.
6. Health Economics; possible advantage of the new rectal preserving treatment in cost per quality of life adjusted life years using the EQ5D score will be analysed. The total costs will be assessed by summing the procedure related costs, in hospital stay costs, reintervention and morbidity related costs and time to return to work will be calculated in loss of work days, which can be converted to costs.
7. Disease free and overall survival at three-year and five-year follow-up.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Prof. dr. J.B. Tuynman

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Prof. dr. J.B. Tuynman

Locations

2 EU/EEA countries · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications