No Operation After Short Course Radiotherapy Followed By Consolidation Chemotherapy In Locally Advanced Rectal Cancer

Rectal Cancer Clinical Trial

— NOAHS-ARC  

Official title:

No Operation After Short Course Equivalent Dose (Ht) Radiation Therapy Followed By Consolidation Chemotherapy In Locally Advanced Rectal Cancer: The Prospective, Single Arm NOAHS-ARC Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04864067
• Other study ID #: FONDECYT 11201291
• Status: Recruiting
• Phase: Phase 2
• Start date: June 9, 2021
• Est. completion date: May 30, 2025

Study information

• Verified date: November 2023
• Source: Servicio de Salud Metropolitano Sur Oriente
• Contact: Felipe F Quezada-Diaz, MD
• Phone: + 562 25762401
• Email: ffquezad[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to explore the hypothesis that in patients with a Locally advanced rectal cancer (LARC) treated with a Total neoadjuvant therapy (TNT) strategy based on short course radiotherapy (5x5Gy) followed by neoadjuvant consolidation chemotherapy is associated with a higher rate of pathological clinical response and sustained (>1year) complete clinical response when compared to an historical cohort treated with long course chemoradiation therapy (CRT), total mesorectal excision (TME) and adjuvant chemotherapy (ACT).

Description:

Non-operative management with a Watch and Wait (W&W) strategy has been advocated for selected patients with a locally advanced rectal cancer (LARC) and a complete clinical response (cCR) after neoajuvant (NA) treatment.

In this context, total neoadjuvant therapy (TNT), i.e the use of radiotherapy and full dose of post-operative chemotherapy as part of NA treatment, has emerged as a strategy to enhance treatment response.

Currently, TNT has reported higher rates of pCR and organ preservation when compared to current standard of care. However, the best TNT strategy is still unknown. We therefore hypothesize that in LARC patients, the use of a TNT strategy based on short course RT followed by consolidation chemotherapy is associated with a higher rate of pCR and sustained (>1year) cCR when compared to an historic cohort.

The main aim of the present proposal is to assess the effects of a standardized TNT model in LARC patients as a strategy for enhanced pCR/sustained cCR. For this purpose, we propose the following experimental model: In primary Aim 1 we will study if the effects of a TNT strategy over patients with a LARC enhance the rate of pCR/sustained cCR by (1) evaluating the compliance and toxicity of a TNT strategy as a proof of concept of its applicability, (2) assessing the rate of cCR at the end of TNT and (3) assessing the rate of pCR in the surgically managed subgroup and sustained cCR (>1year) in the W&W subgroup. Additionally, in primary Aim 2, we will determine if patients with a W&W strategy have better functional outcomes and quality of life (QoL) than patients treated with TME after TNT by (1) using validated questionnaires for the evaluation of bowel, sexual and urinary function for W&W and TME patients and (2) by evaluating the QoL using a widely-used standardized questionnaire.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 73
• Est. completion date: May 30, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of adenocarcinoma of the rectum

• Clinical Stage II (T3-4, N-) or Stage III (any T, N+) based on Magnetic Resonance Imaging (MRI)

• Tumors < 7cm from anal verge (palpable)

• No prior history of rectal cancer

Exclusion Criteria

• Patients with tumors >7cm from anal verge

• ECOG >1,

• Contraindication for chemotherapy: Hemoglobin <8, White Blood Count <4000, Platelets <100,000, Creatinine Clearance <50ml/min, Total Bilirubin <5mg/dl,

• Stage IV at diagnosis

• Coronary artery disease, either no treated or recent acute coronary syndrome in the last 12 months.

• Congestive heart failure

• Peripheral neuropathy

• Previous pelvic radiotherapy

• Prior rectal cancer treatment

• Pregnancy or nursery

• Any contraindications to MRI (e.g. patients with pacemakers)

• Indication of pelvic exenteration

• Impossibility to consent.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Oxaliplatin
Consolidation Chemotherapy
• 5-Fluoracil
Consolidation Chemotherapy
• Leucovorin
Consolidation Chemotherapy
• Capecitabine
Consolidation Chemotherapy

Radiation:
• 5x5 Gy
Neoadjuvant Radiotherapy

Behavioral:
• Quality of Life Questionnaires
Quality of Life Evaluation (LARS Score, IIEF, FSFI, I-PSS and EORTC QLQ-C30)

Procedure:
• DRE/ Endoscopy
Flexible Sigmoidoscopy and Digital Rectal Exam

Locations

Country	Name	City	State
Chile	Complejo Asistencial Doctor Sótero del Rio	Santiago	RM
Chile	Hospital La Florida	Santiago	RM
Chile	Hospital Padre Hurtado	Santiago	RM

Sponsors (1)

Lead Sponsor	Collaborator
Servicio de Salud Metropolitano Sur Oriente

Country where clinical trial is conducted

Chile, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of pathological and sustained clinical response	Combined number of patients with pathological response in the surgical specimen and patients in a Watch and Wait protocol with a sustained clinical response longer than a year.	3 years
Primary	Quality of Life and Funcional Outcomes	Standardized evaluation using validated questionnaires comparing patients undergoing TME versus WW patients in the cohort	3 years
Secondary	Adverse events	Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	3 years