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

NCT04864067 | Completed Phase 2 DMC

• 1 other identifier: FONDECYT 11201291
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Rectal Cancer

Keywords

Rectal Cancer; Radiotherapy; Neoadjuvant therapy; Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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

• Quality of Life and Funcional Outcomes

  Standardized evaluation using validated questionnaires comparing patients undergoing TME versus WW patients in the cohort

  3 years

Secondary Outcomes (1)

• Adverse events

  3 years

Study Arms (1)

Short Course Radiotherapy and Consolidation Chemotherapy

EXPERIMENTAL

This arm will receive short course radiotherapy (5x5 Gy) during 1 week. Between 7 to 14 days after radiotherapy, patient will receive 9 cycles of FOLFOX. CapeOX may be given as alternative for FOLFOX.

Drug: Oxaliplatin; Drug: 5-Fluoracil; Drug: Leucovorin; Drug: Capecitabine; Radiation: 5x5 Gy; Behavioral: Quality of Life Questionnaires; Procedure: DRE/ Endoscopy

Interventions

DRE/ Endoscopy PROCEDURE

Flexible Sigmoidoscopy and Digital Rectal Exam

Short Course Radiotherapy and Consolidation Chemotherapy

Oxaliplatin DRUG

Consolidation Chemotherapy

Also known as: All Brands

Short Course Radiotherapy and Consolidation Chemotherapy

5-Fluoracil DRUG

Consolidation Chemotherapy

Also known as: All Brands

Short Course Radiotherapy and Consolidation Chemotherapy

Leucovorin DRUG

Consolidation Chemotherapy

Also known as: All Brands

Short Course Radiotherapy and Consolidation Chemotherapy

Capecitabine DRUG

Consolidation Chemotherapy

Also known as: All Brands

Short Course Radiotherapy and Consolidation Chemotherapy

5x5 Gy RADIATION

Neoadjuvant Radiotherapy

Short Course Radiotherapy and Consolidation Chemotherapy

Quality of Life Questionnaires BEHAVIORAL

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

Short Course Radiotherapy and Consolidation Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Servicio de Salud Metropolitano Sur Oriente: lead

Study Sites (3)

Complejo Asistencial Doctor Sótero del Rio

Santiago, RM, Chile

Location

Hospital La Florida

Santiago, RM, Chile

Location

Hospital Padre Hurtado

Santiago, RM, Chile

Location

Related Publications (1)

• Quezada-Diaz FF, Bercz A, Escobar JL, Caire N, Diaz-Feldman LE, Manriquez E, Carvajal G. No operation after short-course radiotherapy followed by consolidation chemotherapy in locally advanced rectal cancer (NOAHS-ARC): study protocol for a prospective, phase II trial. Int J Colorectal Dis. 2025 Mar 18;40(1):69. doi: 10.1007/s00384-025-04850-9.

  PMID: 40100473 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms; Adenocarcinoma

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; Capecitabine; Endoscopy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Felipe F Quezada-Diaz, MD

  Complejo Asistencial Doctor Sótero del Rio

  PRINCIPAL INVESTIGATOR

• Nicole M Caire, MD

  Complejo Asistencial Doctor Sótero Del Río

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: The study was designed as a single-arm phase II trial with complete response as the primary endpoint - the composite of pCR after surgery and sustained cCR (≥1 year) during watch-and-wait surveillance. The null hypothesis was a local historical pCR rate of 12% after neoadjuvant chemoradiotherapy plus TME. Assuming an expected complete response rate of 30%, 48 evaluable patients were required for 80% power at a one-sided α of 0.05. A protocol amendment was approved by the Ethics Committee before any interim data were reviewed. It introduced two statistical refinements: a formalized interim analysis using Lan-DeMets α-spending with O'Brien-Fleming boundaries (early efficacy: ≥9/24 responders or p\<.006), and a futility stopping rule to protect patients from a non-beneficial regimen. No changes were made to the endpoint, eligibility, treatment, or follow-up. All amendments were Ethics Committee-approved before investigators reviewed any unblinded data.

Study Record Dates

• First Submitted: April 25, 2021
• First Posted: April 28, 2021
• Study Start: June 9, 2021
• Primary Completion: May 5, 2026
• Study Completion: May 5, 2026
• Last Updated: May 8, 2026

Record last verified: 2026-05

Locations

CL (3)