A Phase 2/3 interventional study of Radiation Therapy and Chemoradiotherapy in Rectal Cancer, Total Neoadjuvant Treatment and Neoadjuvant Therapy, sponsored by National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos. Recruiting at 1 site in Lithuania. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-11.
Sponsored by National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos · Phase 2/3, Interventional, and Treatment
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.
Part One
Inclusion Criteria:
Exclusion Criteria:
Part Two
Inclusion Criteria:
Exclusion Criteria:
Participants in the experimental group will be treated with TNT - CRT plus consolidating Ch. Consolidation Ch lasts 12 weeks. The response to TNT will be assessed 4 to 5 weeks after the last cycle of Ch. Response assessment will be performed through digital examination, pelvic MRI, rectoscopy, and biopsy. Participants will be actively followed up and not treated after a complete or near-complete response. In case of non-response, participants will undergo surgery. If the participant is diagnosed with a near-complete clinical response and wishes to avoid surgery, the response is reassessed after 8 weeks. If there is no response, i.e., near-complete clinical response persists, the participant is offered surgery. Participants in the experimental group do not receive adjuvant treatment after TNT and surgery.
Radiation: Radiation Therapy · Drug: Chemoradiotherapy · Drug: Consolidation Chemotherapy · Procedure: Surgery
In the control group, treatment will start with surgery. Following surgical treatment, adjuvant therapy may be provided for control group participants according to standard clinical practice if indicated.
In the second part of the study, investigators will prospectively collect and analyze the personal medical records of participants who have already received treatment with CRT or TNT. No new diagnostic or therapeutic approaches will be implemented; routine clinical practices for long-term follow-up will continue. For participants who have not received specific treatment and do not meet the inclusion criteria for the first part of the study, as well as those who declined to participate in that part, investigators will follow the routine clinical practices for investigation, treatment, and follow-up as long as they meet the inclusion criteria for the second part of the study.
Other: Part two
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.
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.
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.
Transabdominal Resection: Abdominoperineal resection, low anterior resection, or coloanal anastomosis using total mesorectal excision.
Standard treatment protocols and follow-up procedures are implemented in clinical practice.
If indicated, adjuvant therapy will be administered as usual in clinical practice.
Postoperative complications
Assessed based on the Clavien Dindo classification.
Time frame: From the start of treatment until 3 months after surgery.
TNT toxicity
Local and systemic toxicity and (or) side effects will be recorded according to the general terminology criteria for adverse events version 5.0 (CTCAE v5.0).
Time frame: From the start of treatment until 3 months after TNT.
Mortality rate
Mortality after TNT or surgery.
Time frame: From the start of treatment until 3 months after treatment.
Quality of life
Quality of life Will be assessed using scoring manual of European Organisation For Research And Treatment Of Cancer of CR29 (Colorectal).
Time frame: From the start of treatment until 3 years after treatment.
Low anterior resection syndrome rate.
Assessed based on the LARS questionnaire
Time frame: From the start of treatment until 3 years after treatment.
Fatigue
Fatigue will be assessed using scoring manual of the functional assessment of chronic illness therapy - fatigue (FACIT-F) questionnaire.
Time frame: From the start of treatment until 3 years after treatment
Complete clinical response rate
Criteria for Complete Clinical Response DRE: * Smooth, flat scar * No nodularity Endoscopy: * Pale smooth scar with or without telangiectasia * No ulceration, nodularity, or mucosal irregularities * No stricture MRT: * Fibrotic, linear scar with low signal intensity on T2-weighted images * No diffusion restriction * No suspicious lymph nodes All of the criteria must be satisfied to define a complete clinical response.
Time frame: 12 - 14 weeks after TNT
Near-complete clinical response rate
Near Complete Response DRE: \- Smooth induration or superficial minor mucosal irregularity Endoscopic: * Appearance with irregular small mucosal nodules, superficial ulceration, or mild persistent erythema MRI * Downstaging with or without residual fibrosis, small area of residual signal, and complete or partial regression of lymph nodes * Diffusion-weighted MRI with a small area of residual high signal intensity
Time frame: 12 - 14 weeks after TNT
Rectal preservation rate
Percentage of participants achieving complete or near-complete clinical response and rectal preservation using a "watch and wait" approach.
Time frame: 3 years after TNT
Local regrowth rate
Percentage of participants with tumor regrowth after watch-and-wait when a complete or near-complete clinical response was achieved after TNT
Time frame: 3 years after TNT
Overall survival
The time between enrolment and death from any cause.
Time frame: 3 - 5 years.
Disease-free survival
The time between enrolment and the first documented disease progression, i.e. local recurrence or metastasis, or death from any cause.
Time frame: 3 - 5 years.
Local recurrence-free survival
Local recurrence rates in participants who underwent surgery.
Time frame: 3 - 5 years.
Distant metastasis-free survival
Incidence of distant metastases
Time frame: 3 - 5 years.
Stoma free survival
Stoma-free survival is defined as the period after treatment during which the patient does not develop a stoma.
Time frame: 3 - 5 years.
Plan to share: Undecided
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos