Can we Save the rectum by watchful waiting or transanal surgery following short- or long-course radioTherapy and Additional local oR systemic Treatment for early-stage REctal Cancer?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Radboud universitair medisch centrum Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Oct 2024 → ongoing

Decision date (initial)

2024-08-30

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The assessment of successful organ preservation rates in the concerning study arms.

Secondary objectives 1

1. The toxicity of both additional treatment options, and on functional and oncological outcomes.

Conditions and MedDRA coding

Patients with early-stage rectal cancer (defined as early rectal cancer cT1-3abN0M0 or early-intermediate rectal cancer cT1-3abN1(≤3 nodes ≤8mm)M0

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Biopsy proven adenocarcinoma of the rectum
2. Early- or early-intermediate stage rectal cancer, defined as Magnetic Resonance Imaging (MRI)-T1-3ab, N0/N1 (≤3 mesorectal lymph nodes ≤8mm), MX/M0 rectal tumour
3. Tumour located in the distal or mid-rectum for which TME-surgery is required
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Age 18 years or older
6. Patient able and willing to provide written informed consent for the study

Exclusion criteria 11

1. Concomitant or previous malignancies within 3 years prior to trial entry, except those that in the opinion of the MDT are unlikely to relapse < 3 years or lead to death < 5 years
2. Pre-existing faecal incontinence, leading to an expected impaired quality of life post-treatment
3. Tumour located in the proximal rectum for which PME-surgery will be sufficient
4. MRI suspicious lymph nodes cN1 (1-3 lymph nodes > 8mm) or cN2
5. MRI extramural vascular invasion (mriEMVI) present (defined by protocol guidelines)
6. MRI defined mucinous tumour
7. Mesorectal fascia threatened by tumour (≤ 1mm on MRI)
8. Any form of (endoscopic/surgical) local excision of the primary tumour prior to study-entry
9. Prior pelvic radiotherapy
10. Definite evidence of regional or distant metastases (M1) in opinion of MDT
11. Pregnant or lactating women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the proportion of patients with successful organ preservation at 24 months from the start of treatment.

Secondary endpoints 12

1. Patient- and clinician-reported acute (<3 months following completion of treatment) and late (<1 year following completion of treatment) treatment-related toxicity
2. Proportion of patients with a clinical complete response at 26 weeks (6 months) after onset of treatment
3. Proportion of patients undergoing transanal local excision
4. Complications within the first 30 days after completion or salvage TME-surgery, in terms of postoperatieve morbidity and mortality rates defined by Clavien-Dindo
5. Proportion of patients (in each group) with a stoma at 12 months
6. Time to event of organ loss assessed for patients who prefer organ preservation; defined as the length of time from the start date of trial treatment until TME surgery
7. Regrowth rate at 36 months; defined as endoluminal or locoregional nodal regrowth detected during W&W follow-up
8. Metastasis-free survival to 24 months; defined as the length of time from the start date of trial treatment until death (any cause) or detection of distant metastasis
9. Non-regrowth-disease free survival to 24 months; defined as the length of time from the start of trial treatment until death (any cause), detection of local pelvic recurrence or distant metastasis but not including patients who developed local regrowth which was resected with clear margins using standard TME surgery
10. Overall survival to 36 months; defined as the length of time from the start date of trial treatment until death (any cause)
11. Health Related Quality of Life (HR QoL) standardly measured by EORTC general and colorectal cancer specific quality of life questionnaire (QLQ‐CR29, QLQ‐C30 and EQ-5D-5L) (baseline and at 6 and 24 months); Decision Regret Scale one-time at 24 monts
12. Functional outcome: bowel, bladder and sexual dysfunction measured by low anterior resection syndrome (LARS) score, The International Consultation on Incontinence Modular Questionnaire on Male Lower Urinary Tract Symptoms (ICIQ‐ MLUTS)/ ICIQ‐Female Lower Urinary Tract Symptoms (ICIQ‐FLUTS) questionnaires (baseline and at 6 and 24 months)

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Radboud universitair medisch centrum Stichting

Sponsor organisation

Radboud universitair medisch centrum Stichting

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Radboud universitair medisch centrum / RADBOUDUMC

Contact name

Prof. Hans de Wilt

Public contact point

Organisation

Radboud universitair medisch centrum / RADBOUDUMC

Contact name

dr. Marjan de Vries

Third parties 1

Locations

1 EU/EEA country · 22 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 16 files

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

Application history

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