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

Official title

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

Overview

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.

Interventions

• Radiation 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.
• Drug 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.
• 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.
• Procedure Surgery
  Transabdominal Resection: Abdominoperineal resection, low anterior resection, or coloanal anastomosis using total mesorectal excision.
• Other Part two
  Standard treatment protocols and follow-up procedures are implemented in clinical practice.
• Other Adjuvant treatment
  If indicated, adjuvant therapy will be administered as usual in clinical practice.

Primary outcome measures

• Postoperative complications [Time frame: From the start of treatment until 3 months after surgery.]
• TNT toxicity [Time frame: From the start of treatment until 3 months after TNT.]
• Mortality rate [Time frame: From the start of treatment until 3 months after treatment.]
• Quality of life [Time frame: From the start of treatment until 3 years after treatment.]
• Low anterior resection syndrome rate. [Time frame: From the start of treatment until 3 years after treatment.]
• Fatigue [Time frame: From the start of treatment until 3 years after treatment]
• Complete clinical response rate [Time frame: 12 - 14 weeks after TNT]
• Near-complete clinical response rate [Time frame: 12 - 14 weeks after TNT]

Secondary outcome measures (7)

• Rectal preservation rate [Time frame: 3 years after TNT]
• Local regrowth rate [Time frame: 3 years after TNT]
• Overall survival [Time frame: 3 - 5 years.]
• Disease-free survival [Time frame: 3 - 5 years.]
• Local recurrence-free survival [Time frame: 3 - 5 years.]
• Distant metastasis-free survival [Time frame: 3 - 5 years.]
• Stoma free survival [Time frame: 3 - 5 years.]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Lithuania · 1 center

• Nacional Cancer Institute — Vilnius

Identifiers

NCT: NCT06758830 · STart

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗