Short Course or Long Course Radiotherapy as Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer (SHOOL)

Rajiv Gandhi Cancer Institute & Research Center, India

Status: Not yet enrolling

Conditions: Adenocarcinoma of the Rectum

Treatments: Radiation: SCRT : 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique; Radiation: LCRT + Consolidation Chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07258797

RGCIRC/IRB-BHR/52/2025

Details and patient eligibility

About

This study compares two standard radiotherapy approaches (short-course vs. long-course) given before surgery in patients with locally advanced rectal cancer. The goal is to see which treatment is more effective and better tolerated.

Full description

The SHOOL study is a single-institution, open-label, randomized prospective study designed to evaluate and compare two internationally accepted total neoadjuvant therapy (TNT) strategies in patients with locally advanced rectal cancer (LARC). These strategies differ primarily in their radiotherapy schedule and include:

Arm A: Short-course radiotherapy (SCRT; 25 Gy in 5 fractions over 1 week), followed by consolidation chemotherapy and surgery

Arm B: Long-course chemoradiotherapy (LCRT; 50.4 Gy in 28 fractions with concurrent Capecitabine over 5-5.5 weeks), followed by consolidation chemotherapy and surgery The study acronym "SHOOL" reflects the clinical dilemma of whether SHOrt-course Or Long-course radiotherapy offers better or more practical outcomes when delivered within a TNT framework.

This prospective study aims to explore how these two strategies compare in terms of tumour response (as measured by pathological complete response, pCR), toxicity, treatment compliance, feasibility, quality of life, and local recurrence rates at 3 and 5 years. Given that both arms represent evolving standards of care, this study is designed to generate real-world data that can guide institutional decision-making and inform future definitive trials.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically confirmed adenocarcinoma of the rectum
2. Locally advanced disease based on MRI including cT3-T4 and/or node positive disease (cN1 or N2)
3. Tumor located within 15 cm from the anal verge (confirmed by endoscopy or MRI)
4. ECOG performance status 0-2
5. Hemoglobin ≥ 9 g/dL
6. Absolute neutrophil count ≥ 1,500/mm³
7. Platelets ≥ 100,000/mm³
8. Total bilirubin ≤ 1.5 × ULN
9. Aspartate transaminase/Alanine transaminase ≤ 2.5 × ULN
10. Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min
11. Fit for neoadjuvant therapy and curative resection
12. Willing and able to provide written, informed consent
13. Baseline MRI and biopsy (even if done outside) must be reviewed and approved by the institutional radiology and pathology review board, requiring concurrence from two independent pathologists and two independent radiologists

Exclusion criteria

1. Metastatic disease at presentation (distant nodes, liver, lung, peritoneum, etc.)
2. Prior pelvic radiotherapy or systemic chemotherapy for rectal cancer
3. Presence of synchronous malignancies or previous malignancy within 5 years except: Treated basal cell or squamous cell carcinoma of the skin, In situ cervical cancer, Active uncontrolled infection
4. Known HIV infection with CD4 < 200 cells/μL, or active hepatitis B or C
5. Severe comorbid conditions precluding therapy (e.g., decompensated cardiac, hepatic, or renal disease)
6. Pregnant or breastfeeding women
7. Inability to comply with protocol requirements or follow-up schedule
8. Psychiatric illness or social situations that may limit compliance with study requirements

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

SCRT + Consolidation Chemotherapy

Active Comparator group

Description:

Radiotherapy: 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique. 1. Interval before Chemotherapy: 1-2 weeks after completion of radiotherapy. 2. Chemotherapy: Modified FOLFOX6 every 2 weeks (total of 12 cycles).

Treatment:

Radiation: SCRT : 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique

LCRT + Consolidation Chemotherapy

Active Comparator group

Description:

Radiotherapy: 1. Primary tumor and involved nodes: 50 Gy in 25 fractions. 2. Elective nodal basin: 45 Gy in 25 fractions. Delivered concurrently with oral Capecitabine (825 mg/m² twice daily on radiotherapy days).

Treatment:

Radiation: LCRT + Consolidation Chemotherapy