Clinical trial NCT06758830: Total Neoadjuvant Therapy and Organ Preservation Versus Surgery for Rectal Cancer.
Official title: Total Neoadjuvant Therapy for Rectal Cancer - a New Standard of Care?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
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
Keywords: Rectal cancer
Total Neoadjuvant Treatment
Neoadjuvant therapy
Radiotherapy
Chemotherapy
Chemoradiotherapy
Organ Preservation
Radiotherapy Side Effect
Chemotherapy side effects
Quality of Lifte
Fatigue
Postoperative complications
Low Anterior Resection Syndrome
Lead sponsor: National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos
Sponsor class: OTHER
Collaborators: name: Vilnius University
name: Tomas Poskus, Faculty of Medicine, Vilnius University
name: Vilnius University Hospital Santaros Klinikos
name: Research Council of Lithuania
First posted: 2025-01-06
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: \*\*Part One:\*\* A prospective randomized study. Participants will be randomly divided into two groups: an experimental group and a control group.

\*\*Part Two:\*\* A prospective cohort study. In the second part of the study, there is no planned allocation of groups.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Postoperative complications
timeFrame: From the start of treatment until 3 months after surgery.
measure: TNT toxicity
timeFrame: From the start of treatment until 3 months after TNT.
measure: Mortality rate
timeFrame: From the start of treatment until 3 months after treatment.
measure: Quality of life
timeFrame: From the start of treatment until 3 years after treatment.
measure: Low anterior resection syndrome rate.
timeFrame: From the start of treatment until 3 years after treatment.
measure: Fatigue
timeFrame: From the start of treatment until 3 years after treatment
measure: Complete clinical response rate
timeFrame: 12 - 14 weeks after TNT
measure: Near-complete clinical response rate
timeFrame: 12 - 14 weeks after TNT
Secondary outcomes:
measure: Rectal preservation rate
timeFrame: 3 years after TNT
measure: Local regrowth rate
timeFrame: 3 years after TNT
measure: Overall survival
timeFrame: 3 - 5 years.
measure: Disease-free survival
timeFrame: 3 - 5 years.
measure: Local recurrence-free survival
timeFrame: 3 - 5 years.
measure: Distant metastasis-free survival
timeFrame: 3 - 5 years.
measure: Stoma free survival
timeFrame: 3 - 5 years.
Other outcomes:
Locations:
city: Vilnius
country: Lithuania
facility: Nacional Cancer Institute
Study officials:
affiliation: Translational Health Research Institute, Faculty of Medicine, Vilnius University Ciurlionio str. 21, LT-03101 Vilnius
name: Tomas Poškus, PhD
role: STUDY_CHAIR
affiliation: General and Abdominal Surgery and Oncology Department, National Cancer Institute, Vilnius, Lithuania
name: Audrius Dulskas, PhD
role: PRINCIPAL_INVESTIGATOR
References: