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

NCT ID: NCT06758830

Last Updated: 2025-01-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-07
• Study Completion Date: 2029-12-27

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Part one. The first group: an experimental group - TNT, organ preservation.

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.

Group Type: EXPERIMENTAL

Radiation Therapy

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: PROCEDURE

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

Part one. Second Group: a control Group - 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.

Group Type: ACTIVE_COMPARATOR

Surgery

Intervention Type: PROCEDURE

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

Adjuvant treatment

Intervention Type: OTHER

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

Part two of the study

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.

Group Type: OTHER

Part two

Intervention Type: OTHER

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

Interventions

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.

Intervention Type: RADIATION

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.

Intervention Type: 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.

Intervention Type: DRUG

Surgery

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

Intervention Type: PROCEDURE

Part two

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

Intervention Type: OTHER

Adjuvant treatment

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

Intervention Type: OTHER

Eligibility Criteria

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.

• 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 have received preoperative CRT or TNT or are in the planning stages of neoadjuvant treatment.

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vilnius University

OTHER

Sponsor Role: collaborator

Tomas Poskus, Faculty of Medicine, Vilnius University

UNKNOWN

Sponsor Role: collaborator

Vilnius University Hospital Santaros Klinikos

OTHER

Sponsor Role: collaborator

Research Council of Lithuania

OTHER

Sponsor Role: collaborator

National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tomas Poškus, PhD

Role: STUDY_CHAIR

Translational Health Research Institute, Faculty of Medicine, Vilnius University Ciurlionio str. 21, LT-03101 Vilnius

Audrius Dulskas, PhD

Role: PRINCIPAL_INVESTIGATOR

General and Abdominal Surgery and Oncology Department, National Cancer Institute, Vilnius, Lithuania

Locations

Nacional Cancer Institute

Vilnius, , Lithuania

Site Status: RECRUITING

Countries

Lithuania

Central Contacts

Ernestas Šileika, MD

Role: CONTACT

ernestas.sileika@nvc.santa.lt

+37060950402

Audrius Dulskas, PhD

Role: CONTACT

audrius.dulskas@gmail.com

+370 675 20094

Facility Contacts

Ernestas Šileika, MD

Role: primary

ernestas.sileika@nvc.santa.lt

+37060950402

Audrius Dulskas, PhD

Role: backup

audrius.dulskas@gmail.com

+37067520094

Tomas Poškus, PhD

Role: backup

Audrius Dulskas, PhD

Role: backup

Ernestas Šileika, MD

Role: backup

Other Identifiers

STart

Identifier Type: -

Identifier Source: org_study_id