Neoadjuvant Chemoradiotherapy Versus Total Neoadjuvant Therapy in the Treatment of T3 Rectal Cancer

Phase 3

Not yet recruiting

• Conditions: Rectal Cancer
• Interventions: Drug: Neoadjuvant Chemoradiotherapy; Drug: Total Neoadjuvant Therapy

• Registration Number: NCT06097416
• Lead Sponsor: St. James's Hospital, Ireland

Brief Summary

The gold standard treatment for locally advanced, non-metastatic rectal cancer includes neoadjuvant chemoradiotherapy (NACRT), total mesorectal excision (TME) and adjuvant chemotherapy (AC). The primary goal of treatment is to achieve local disease control, reduce tumour volume and minimise the risk of distant metastases. While this multimodal treatment approach has offered improvements in local control and sphincter preservation, it has had little effect on distant recurrence and overall survival. We aim to compare NACRT and TME using the following endpoints:

Primary --\>To compare the effects neoadjuvant chemoradiotherapy versus total neoadjuvant therapy (TNT) for T3 rectal cancer on overall survival.

Secondary --\> To compare the effects neoadjuvant chemoradiotherapy (NARCT) and total neoadjuvant therapy (TNT) for cT3 rectal cancer on clinical outcomes:

* Clinical complete response (cCR)

* Pathological complete response (pCR)

* Disease-free survival (DFS)

* Organ preservation

* Overall morbidity / mortality

* Treatment-related morbidity / mortality

* Peri-operative outcomes

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-10
• Study First Submitted: 2023-10-18
• Study First Submitted QC: 2023-10-18
• Study First Posted: 2023-10-24
• Last Update Submitted: 2023-10-24
• Last Update Posted: 2023-10-25
• Study Start: 2024-10
• Primary Completion: 2025-10
• Study Completion: 2030-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neoadjuvant chemoradiotherapy	Neoadjuvant Chemoradiotherapy	The NARCT regimen is prescribed specifically as standard 5-FU over several weeks. The CRT regimen consists of the standard algorithms: a total of 5400-5600 cGy of radiation (4500 cGy to the pelvis, with an integrated boost to the primary tumour and involved nodes of 500 cGy followed by an option boost to the primary tumour and involved nodes) delivered in 27-28 fractions, respectively, of 180-200 cGy each over a 5-6 week period.
Total Neoadjuvant Therapy	Total Neoadjuvant Therapy	Sequence of TNT regimen can be classified as induction (chemotherapy first) or consolidation (radiation first) treatment. All patients received the same chemotherapy (FOLFOX) and long-course chemoradiotherapy (50.4 Gy in 28 fractions) before surgery. However timing of TNT can differ depending on concerns of local and distal failure.

Primary Outcome Measures

Name	Time	Method
Overall survival	Five years	Alive

Secondary Outcome Measures

Name	Time	Method
Clinical complete response	6 months	No residual tumour visible on imaging
Pathological complete response	6 months	Absence of residual invasive or in situ tumour on biopsy / resected specimen.
Disease-free survival	5 years	Measure of time after treatment where no evidence of disease is found.
Progression-free survival	5 years	Time from randomisation to occurrence of disease progression or death