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

National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos

Status and phase: Enrolling; Phase 3; Phase 2

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

Treatments: Other: Part two; Drug: Chemoradiotherapy; Drug: Consolidation Chemotherapy; Radiation: Radiation Therapy; Procedure: Surgery; Other: Adjuvant treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT06758830

STart

Details and patient eligibility

About

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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400 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

Procedure: Surgery

Radiation: Radiation Therapy

Drug: Consolidation Chemotherapy

Drug: Chemoradiotherapy

Part one. Second Group: a control Group - surgery

Active Comparator group

Description:

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.

Treatment:

Other: Adjuvant treatment

Procedure: Surgery

Part two of the study

Other group

Description:

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.

Treatment:

Other: Part two