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

NCT07258797 | Not Yet Recruiting DMC

• 1 other identifier: RGCIRC/IRB-BHR/52/2025
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adenocarcinoma of the Rectum

Keywords

SHORT COURSE RADIOTHERAPY; LONG COURSE RADIOTHERAPY; RECTAL CANCER; OUTCOMES; SURVIVAL

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate measured in proportion of participants (%)

  Proportion of participants achieving pathological complete response, defined as ypT0N0 on histopathological examination of resected tumor specimens after surgery. Assessment will be performed by institutional pathologists according to standardized reporting guidelines. The pCR rate is central to evaluating early tumor response to total neoadjuvant therapy. Unit of Measure: Proportion of participants (%)

  3 and 5 years

Secondary Outcomes (6)

• Local Recurrence Rate measured in percentage of participants (%)

  3 and 5 years

• Overall Survival (OS) in months

  Evaluated at 3 years and 5 years

• Acute Toxicities graded using CTCAE version 5.0

  3 months post surgery

• Late Toxicities documented using clinician assessment and patient reported outcomes EORTC QLQ-C30 and QLQ-CR29

  6 months to 2 years post-treatment

• Treatment completion Rate measured in percentage of participants (%)

  1 year

Study Arms (2)

SCRT + Consolidation Chemotherapy

ACTIVE COMPARATOR

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).

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

LCRT + Consolidation Chemotherapy

ACTIVE COMPARATOR

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).

Radiation: LCRT + Consolidation Chemotherapy

Interventions

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

Arm A - SCRT + Consolidation Chemotherapy 1. Radiotherapy: 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique. 2. Interval before Chemotherapy: 1-2 weeks after completion of radiotherapy. 3. Chemotherapy: Modified FOLFOX6 every 2 weeks (total of 12 cycles). If the patient is fit, the option of intensifying the chemo to mFOLFIRINOX will be discussed with the patient

SCRT + Consolidation Chemotherapy

LCRT + Consolidation Chemotherapy RADIATION

Arm B - LCRT + Consolidation Chemotherapy 1) Radiotherapy: o Primary tumor and involved nodes: 50 Gy in 25 fractions. o Elective nodal basin: 45 Gy in 25 fractions. Delivered concurrently with oral Capecitabine (825 mg/m² twice daily on radiotherapy days). o Technique: IGRT 2) Interval before Chemotherapy: 1-2 weeks after completion of chemoradiotherapy. 3) Chemotherapy: Modified FOLFOX6

LCRT + Consolidation Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the rectum
• Locally advanced disease based on MRI including cT3-T4 and/or node positive disease (cN1 or N2)
• Tumor located within 15 cm from the anal verge (confirmed by endoscopy or MRI)
• ECOG performance status 0-2
• Hemoglobin ≥ 9 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• Platelets ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 × ULN
• Aspartate transaminase/Alanine transaminase ≤ 2.5 × ULN
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min
• Fit for neoadjuvant therapy and curative resection
• Willing and able to provide written, informed consent
• 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

You may not qualify if:

• Metastatic disease at presentation (distant nodes, liver, lung, peritoneum, etc.)
• Prior pelvic radiotherapy or systemic chemotherapy for rectal cancer
• 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
• Known HIV infection with CD4 \< 200 cells/μL, or active hepatitis B or C
• Severe comorbid conditions precluding therapy (e.g., decompensated cardiac, hepatic, or renal disease)
• Pregnant or breastfeeding women
• Inability to comply with protocol requirements or follow-up schedule
• Psychiatric illness or social situations that may limit compliance with study requirements

Sponsors & Collaborators

• Rajiv Gandhi Cancer Institute & Research Center, India: lead

Study Sites (1)

Rajiv Gandhi Cancer Institute and Research Centre

New Delhi, 110085, India

Location

Related Publications (1)

• Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. doi: 10.1016/S1470-2045(20)30555-6. Epub 2020 Dec 7.

  PMID: 33301740 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Consolidation Chemotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Jaskaran Sethi, MD

  Rajiv Gandhi Cancer Hospital and Research Centre, New Delhi

  STUDY DIRECTOR

Central Study Contacts

Shivendra Singh, MCh

CONTACT

919818975024; drshivendraonco@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant, Department of Gastrointestinal and Hepatobiliary services

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 2, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: IPD and supporting information will be available beginning six months after publication of the primary results or completion of the study, whichever is later. Data will remain accessible for five years from the start date of availability.
• Access Criteria: Qualified researchers who submit a methodologically sound research proposal will be able to access de-identified individual participant data underlying the main results, as well as supporting documents such as the study protocol and statistical analysis plan. Access will be granted through a secure data sharing portal, subject to data use agreements that ensure participant confidentiality and limit use to the specified research purpose

Locations

IN (1)