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NCT Number: NCT06758830

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

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.

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Key information

Conditions

Rectal Cancer Chemoradiotherapy Chemotherapy Chemotherapy Side Effects Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Fatigue Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Low Anterior Resection Syndrome Neoadjuvant Therapy Neoplasms Neoplasms by Site Organ Preservation Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Quality of Life Radiation Injuries Radiotherapy Radiotherapy Side Effect Rectal Diseases Rectal Neoplasms Signs and Symptoms Total Neoadjuvant Treatment Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Nacional Cancer Institute

Vilnius, 08660, Lithuania

Location status: Recruiting

Location contact

Audrius Dulskas, PhD

CONTACT

[email protected]

+37067520094

Audrius Dulskas, PhD

PRINCIPAL_INVESTIGATOR

Ernestas Šileika, MD

CONTACT

[email protected]

+37060950402

Ernestas Šileika, MD

SUB_INVESTIGATOR

Tomas Poškus, PhD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Part One

Inclusion criteria

  • Over 18 years of age.
  • Participants who agreed to participate in the study signed an informed consent form.
  • The Eastern Cooperative Oncology Group (ECOG) score ranges from 0 to 2.
  • Pathologically confirmed rectal adenocarcinoma.
  • Tumor up to 10 cm from the anus.
  • Magnetic resonance imaging (MRI) of the pelvis and computed tomography (CT) of the thorax and abdomen were performed to confirm the diagnosis.
  • cT1N1, T2-T3 N0 - 1, M0, MRF -, EMVI -.
  • Normal bone marrow function: blood leucocytes > 3.5 × 10⁹/l, neutrophils > 1.5 × 10⁹/l, platelets > 100 × 10⁹/l.
  • Normal renal function: creatinine within 1,5 × normal.
  • Normal liver function: blood bilirubin levels within 1,5 times normal, AST, ALT levels within 2,5 times the upper limit.

Exclusion criteria

  • Prior ST or Ch.
  • Participants who are not eligible for pelvic MRI.
  • Participants who have had a malignancy in the last 5 years, except for treatment for basal cell or squamous cell skin cancer or in situ cervical cancer.
  • ECOG status ≥ 3.
  • Distant metastases detected.
  • Participants with uncontrolled therapeutic or psychiatric conditions.
  • Infectious diseases requiring antibiotic treatment.

Part Two

Inclusion criteria

  • Over 18 years of age.
  • Participants who agreed to participate in the study signed an informed consent form.
  • ECOG score between 0 and 2.
  • Pathological confirmed rectal adenocarcinoma.
  • Stage I to III rectal cancer confirmed.
  • The tumor is localized up to 12 cm from the anus.
  • Participants who refused to participate in the first part of the study or did not meet the inclusion criteria for the first part.
  • Participants have received preoperative CRT or TNT or are in the planning stages of neoadjuvant treatment.

Exclusion criteria

  • New cancer two years after CRT.
  • Stage IV cancer before treatment.
  • Participants refusing to participate in the study or unable to sign the informed consent.

Treatment and study plan

radiation therapy

Radiation

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.

Chemoradiotherapy

Drug

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.

Consolidation Chemotherapy

Drug

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.

Surgery

Procedure

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

Part two

Other

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

Adjuvant treatment

Other

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

Primary outcomes

  1. Postoperative complications

    Time frame: From the start of treatment until 3 months after surgery.

    Assessed based on the Clavien Dindo classification.

  2. TNT toxicity

    Time frame: From the start of treatment until 3 months after TNT.

    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).

  3. Mortality rate

    Time frame: From the start of treatment until 3 months after treatment.

    Mortality after TNT or surgery.

  4. Quality of life

    Time frame: From the start of treatment until 3 years after treatment.

    Quality of life Will be assessed using scoring manual of European Organisation For Research And Treatment Of Cancer of CR29 (Colorectal).

  5. Low anterior resection syndrome rate.

    Time frame: From the start of treatment until 3 years after treatment.

    Assessed based on the LARS questionnaire

  6. Fatigue

    Time frame: From the start of treatment until 3 years after treatment

    Fatigue will be assessed using scoring manual of the functional assessment of chronic illness therapy - fatigue (FACIT-F) questionnaire.

  7. Complete clinical response rate

    Time frame: 12 - 14 weeks after TNT

    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.

  8. Near-complete clinical response rate

    Time frame: 12 - 14 weeks after TNT

    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

Secondary outcomes

  1. Rectal preservation rate

    Time frame: 3 years after TNT

    Percentage of participants achieving complete or near-complete clinical response and rectal preservation using a "watch and wait" approach.

  2. Local regrowth rate

    Time frame: 3 years after TNT

    Percentage of participants with tumor regrowth after watch-and-wait when a complete or near-complete clinical response was achieved after TNT

  3. Overall survival

    Time frame: 3 - 5 years.

    The time between enrolment and death from any cause.

  4. Disease-free survival

    Time frame: 3 - 5 years.

    The time between enrolment and the first documented disease progression, i.e. local recurrence or metastasis, or death from any cause.

  5. Local recurrence-free survival

    Time frame: 3 - 5 years.

    Local recurrence rates in participants who underwent surgery.

  6. Distant metastasis-free survival

    Time frame: 3 - 5 years.

    Incidence of distant metastases

  7. Stoma free survival

    Time frame: 3 - 5 years.

    Stoma-free survival is defined as the period after treatment during which the patient does not develop a stoma.

Study contacts

Contact information is provided by the study sponsor or research team.

Audrius Dulskas, PhD

CONTACT

[email protected]

+370 675 20094

Ernestas Šileika, MD

CONTACT

[email protected]

+37060950402

Sponsors and collaborators

Lead sponsor

National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos

Other

Collaborators

  • Research Council of Lithuania
  • Tomas Poskus, Faculty of Medicine, Vilnius University
  • Vilnius University
  • Vilnius University Hospital Santaros Klinikos

Registry information

Official study title

Total Neoadjuvant Therapy for Rectal Cancer - a New Standard of Care?

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Jan 6, 2025
Registry last updated
May 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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