Total Neoadjuvant Therapy and Organ Preservation Versus Surgery for Rectal Cancer.

Summary

This study hypothesizes that approximately 50% of rectal cancer patients can preserve their rectum using a watch-and-wait strategy if they achieve a complete or near-complete clinical response to total neoadjuvant therapy (TNT). The objective is to determine whether the complications, quality of life, and survival rates of rectal cancer patients who have achieved a complete or near-complete clinical response to TNT, followed by a watch-and-wait approach, are comparable to those of patients who undergo surgery first. Additionally, the study aims to identify potential prognostic and predictive markers for rectal cancer and examine survival rates and factors influencing responses to chemoradiotherapy (CRT) or TNT.

The study is divided into two parts:

\*\*Part One:\*\* Participants with cT1N1, T2-T3 N0-1 rectal cancer, MRF-, and EMVI-, with surgery as one of the possible first-line treatment options, will be randomized into two groups. The experimental group will consist of participants receiving TNT, including CRT and consolidation chemotherapy (Ch). If these participants achieve a complete or near-complete clinical response, they will be observed using a watch-and-wait strategy, which is a non-operative approach. The control group will consist of participants who undergo surgical treatment initially.

\*\*Part Two:\*\* All participants with rectal cancer who have received CRT or TNT will be included. Additionally, participants diagnosed with rectal cancer who are scheduled for CRT or TNT but declined to participate in Part One or do not meet the inclusion criteria will also be included.

Conditions

• Rectal Cancer
• Total Neoadjuvant Treatment
• Neoadjuvant Therapy
• Radiotherapy
• Chemotherapy
• Organ Preservation
• Radiotherapy Side Effect
• Chemotherapy Side Effects
• Chemoradiotherapy
• Low Anterior Resection Syndrome
• Quality of Life

Interventions

RADIATION

Radiation Therapy

Radiation therapy (RT) is administered at a dose of 2 Gy per day for a total dose of 50 Gy delivered to the pelvis. This is done throughout 5 to 6 weeks.

DRUG

Chemoradiotherapy

Capecitabine: 825 mg/m² twice daily, prescribed 1-5 days per week, for 5 weeks during RT. Or Bolus 5-FU regimen: 5-fluorouracil (5-FU) 400 mg/m2/day intravenously, administered on days 1-4 and 33-35. Calcium folinate (folinic acid) 20 mg/m2/day intravenously on days 1-4 and 33-35.

DRUG

Consolidation Chemotherapy

XELOX: Oxaliplatin 130 mg/m² (day 1) + capecitabine 1000 mg/m² (days 1-14), every 3 weeks for 4 cycles. Or FOLFOX: Oxaliplatin - 85 mg/m2 intravenously (2-hour infusion), drip for 1 day. Calcium folinate (folinic acid) - 400 mg/m2/d. intravenously (2-hour infusion), started on day 1. F(5-fluorouracil) - 400 mg/m2/d. intravenously (bolus), started on day 1. Repeat every 2 weeks for 6 times.

PROCEDURE

Surgery

Transabdominal Resection: Abdominoperineal resection, low anterior resection, or coloanal anastomosis using total mesorectal excision.

OTHER

Part two

Standard treatment protocols and follow-up procedures are implemented in clinical practice.

OTHER

Adjuvant treatment

If indicated, adjuvant therapy will be administered as usual in clinical practice.

Sponsors & Collaborators

• Vilnius University

  collaborator OTHER

• Tomas Poskus, Faculty of Medicine, Vilnius University

  collaborator UNKNOWN

• Vilnius University Hospital Santaros Klinikos

  collaborator OTHER

• Research Council of Lithuania

  collaborator OTHER

• National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos

  lead OTHER

Principal Investigators

• Tomas Poškus, PhD · Translational Health Research Institute, Faculty of Medicine, Vilnius University Ciurlionio str. 21, LT-03101 Vilnius

• Audrius Dulskas, PhD · General and Abdominal Surgery and Oncology Department, National Cancer Institute, Vilnius, Lithuania

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-06

Primary Completion

2029-12-27

Completion

2029-12-27

Countries

• Lithuania

Study Locations