Next Generation STAR-TREC (NG-ST) - Organ Preservation in Early Rectal Cancer (NG-ST)

Next Generation STAR-TREC: A Prospective Multicenter Study Evaluating Organ Preservation With Mesorectal Chemoradiotherapy in Early Rectal Cancer

This study evaluates whether mesorectal chemoradiotherapy with a limited radiation target volume can achieve a sustained clinical complete response in patients with early-stage rectal cancer, allowing surgery to be safely deferred. Patients may choose between standard total mesorectal excision (TME) surgery or organ preservation with chemoradiotherapy followed by structured surveillance. The study aims to assess oncologic safety, organ preservation rates, and quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Combination product: Capecitabine + Radiotherapy; Procedure: Total Mesorectal Excision (TME)

Detailed Description

Background and Rationale

Standard treatment for early-stage rectal cancer is total mesorectal excision (TME), which provides good oncologic control but may result in substantial functional morbidity. Even in early tumors, radical surgery can lead to bowel dysfunction (including low anterior resection syndrome), urinary and sexual dysfunction, and in some cases permanent stoma formation. While oncologic outcomes are generally favorable, the long-term impact on quality of life remains significant for many patients.

Neoadjuvant chemoradiotherapy (CRT) has been shown to induce tumor regression in rectal cancer, and in a subset of patients a clinical complete response (cCR) may be achieved. In such cases, surgery may potentially be deferred under strict surveillance protocols, a strategy often referred to as organ preservation or "watch and wait." Previous prospective and international studies, including STAR-TREC, have demonstrated promising rates of clinical complete response in selected patients with early rectal tumors.

Study Objectives

Primary Objective To determine whether mesorectal chemoradiotherapy (50 Gy in 25 fractions combined with capecitabine 825 mg/m² twice daily on radiotherapy days) can achieve a sustained clinical complete response at one year in patients with early rectal cancer, allowing surgery to be safely deferred.

Secondary Objectives

• To evaluate local recurrence and local regrowth rates
• To assess distant metastases and overall survival
• To evaluate organ preservation rates at 3 years
• To assess surgical morbidity (if surgery is performed)
• To evaluate patient-reported outcomes including quality of life, bowel function, urinary function, and sexual function
• To perform health economic evaluation

Study Design

NG-ST is a national, multicenter, prospective, non-randomized phase IV cohort study conducted under EU Regulation 536/2014 (CTR). The study is classified as a low-intervention clinical trial, as capecitabine is an authorized medicinal product used within its marketing authorization, albeit at an earlier tumor stage than standard routine.

Eligible patients have biopsy-confirmed rectal adenocarcinoma ≤12 cm from the anal verge and MRI-staged T1-T3b, N0/NX, M0 disease. Both TME surgery and chemoradiotherapy must be considered feasible treatment options by the multidisciplinary team (MDT).

Patients are offered a choice between standard upfront TME surgery and organ preservation with mesorectal chemoradiotherapy.

Interventions

Organ Preservation Arm Radiotherapy: 50 Gy delivered in 25 fractions (2 Gy per fraction), 5 days per week over 5 weeks.

Capecitabine: 825 mg/m² orally twice daily on radiotherapy days.

Structured response assessment is performed 6-8 weeks after completion of CRT using MRI, endoscopy, and clinical examination. Patients achieving clinical complete response enter a structured surveillance program. Patients without complete response proceed to TME surgery.

Standard Surgery Arm Patients undergo total mesorectal excision (TME) according to local standards. Surgical approach is at the discretion of the treating surgeon.

Definition of Clinical Complete Response

• No residual tumor or suspicious lymph nodes on MRI
• No visible tumor on endoscopy (scar or fibrosis permitted)
• No palpable tumor on digital rectal examination

Follow-Up

Patients are followed prospectively with structured surveillance including MRI, endoscopy, clinical examination, and quality-of-life questionnaires. Follow-up continues for at least three years, with longer-term survival assessment up to five years.

Safety Monitoring

Adverse events (AE), serious adverse events (SAE), and suspected unexpected serious adverse reactions (SUSAR) are recorded and reported according to EU CTR requirements. Annual Safety Reports are submitted via CTIS in accordance with Article 43 of Regulation (EU) 536/2014.

Significance

The NG-ST study aims to prospectively evaluate an organ-preserving strategy that may reduce the need for radical surgery and improve long-term functional outcomes without compromising oncologic safety in selected patients with early rectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eva Angenete, MD, PhD; Phone Number: +46-31-342-10-00; Email: eva.angenete@gu.se
• Study Contact Backup: Name: Jennifer Park, MD, PhD; Email: jennifer.park@gu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Written informed consent
• Biopsy-proven rectal adenocarcinoma
• Tumor located <12 cm from the anal verge
• MRI-staged T1-T3b tumor
• N0 or NX (no radiologic evidence of nodal metastases)
• M0 or MX (no radiological evidence of distant metastases)
• ECOG performance status 0-1
• Multidisciplinary team (MDT) assessment confirming that both total mesorectal excision (TME) and chemoradiotherapy are feasible treatment options

Exclusion Criteria:

• MRI-defined N1 or higher nodal disease
• Distant metastases (M1)
• MRI extramural vascular invasion (mriEMVI)
• Threatened mesorectal fascia (≤1 mm on MRI)
• Maximum tumor diameter > 40 mm
• MRI defined mucinous tumor
• No residual luminal tumor following prior endoscopic resection
• Recurrent rectal cancer
• Prior pelvic radiotherapy
• Uncontrolled significant cardiorespiratory comorbidity
• Known complete dihydropyrimidine dehydrogenase (DPYD) deficiency
• Known Gilbert's syndrome
• Pregnancy or breastfeeding
• Concomitant medication contraindicated with capecitabine that cannot be safely discontinued
• Age <18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesorectal chemoradiotherapy; Participants receive mesorectal chemoradiotherapy consisting of radiotherapy (50 Gy in 25 fractions over 5 weeks) combined with capecitabine 825 mg/m² orally twice daily on radiotherapy days. Treatment response is assessed 6-8 weeks after completion using high-resolution MRI, endoscopy, and clinical examination. Participants achieving clinical complete response enter a structured "watch and wait" surveillance program with regular MRI, endoscopy, and clinical follow-up. If incomplete response or tumor regrowth is detected at any time during surveillance, total mesorectal excision (TME) surgery is recommended according to standard of care.	Combination product: Capecitabine + Radiotherapy; Capecitabine is administered orally at a dose of 825 mg/m² twice daily on radiotherapy treatment days (5 days per week) during the 5-week course of mesorectal radiotherapy. External beam radiotherapy is delivered to the primary tumor and surrounding mesorectum at a total dose of 50 Gy in 25 fractions (2 Gy per fraction), administered once daily, 5 days per week, over approximately 5 weeks, according to protocol-defined target volumes.
Active Comparator: Standard Surgery (Total Mesorectal Excision); Participants undergo upfront total mesorectal excision (TME) according to standard surgical practice and national guidelines for early rectal cancer. The surgical approach (open, laparoscopic, or robotic) is at the discretion of the treating surgeon. No neoadjuvant radiotherapy is administered. Postoperative care and oncologic follow-up are conducted according to national guidelines. Participants contribute clinical, oncologic, and patient-reported outcome data for comparison with the organ preservation arm.	Procedure: Total Mesorectal Excision (TME); Total mesorectal excision (TME) is performed according to standard surgical practice for rectal cancer. The surgical approach (open, laparoscopic, or robotic) is determined by the treating surgeon in accordance with local guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained clinical complete response at 1 year	Proportion of participants in the organ preservation arm who achieve a clinical complete response (cCR) and remain without surgical resection at 1 year after initiation of treatment. Clinical complete response is defined by absence of residual tumor on MRI, no visible tumor on endoscopy (scar/fibrosis permitted), and no palpable tumor on clinical examination.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Complete Response at 3 Years	Proportion of participants achieving and maintaining clinical complete response without surgical resection at 3 years.	3 years
Local Recurrence Rate	Proportion of participants developing local recurrence after initial treatment.	3 years
Distant metastases	Proportion of participants developing distant metastatic disease.	3 years
Overall Survival	Overall survival measured from study inclusion to death from any cause.	up to 5 years
Organ Preservation Rate	Proportion of participants with preserved rectum without permanent stoma at 3 years.	3 years
Surgical Morbidity	Postoperative complications measured using the Comprehensive Complication Index (CCI) in participants undergoing surgery.	Within 90 days after surgery
Total Length of Hospital Stay	Total number of days hospitalized, including readmissions, within the first year after diagnosis.	Within 1 year after diagnosis
Patient reported quality of life	Quality of life will be measured using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C30. Scores range from 0-100, with higher scores representing better functioning and global health status but worse symptoms on symptom scales.	up to 3 years
Patient reported quality of life	Quality of life related to colorectal cancer will be assessed using the European Organisation for Research and Treatment of Cancer colorectal cancer module (EORTC QLQ-CR29). Scores are linearly transformed to a 0-100 scale; higher scores on functional scales indicate better functioning, whereas higher scores on symptom scales indicate greater symptom burden.	up to 3 years
Bowel function	Low Anterior Resection Syndrome will be assessed using the Low Anterior Resection Syndrome (LARS) Score, a validated patient-reported outcome measure evaluating bowel dysfunction after rectal cancer surgery. Scores range from 0 to 42, with higher scores indicating more severe bowel dysfunction (0-20 = no LARS, 21-29 = minor LARS, 30-42 = major LARS).	Up to 3 years

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Skane University Hospital; Stockholm South General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 12, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: quality of life; chemoradiotherapy; organ preservation; clinical complete response; watch and wait; Early rectal cancer; low anterior resection syndrom
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Radiotherapy
• Other Study ID Numbers: 2025-522955-25-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No