Adaptive Boost Radiotherapy to Primary Lesions and Positive Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer

NCT06246344 | Active Not Recruiting Phase 3

• 1 other identifier: SDZLEC2023-390-02
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-center, randomized controlled trial evaluates whether online adaptive radiotherapy (ART) with a sequential boost to both the primary rectal tumor and clinically involved lymph nodes improves pathologic complete response in patients with high-risk, node-positive locally advanced rectal cancer. Participants were randomly assigned 1:1 to online ART with a sequential boost or conventional non-adaptive intensity-modulated radiotherapy (IMRT). Both groups received concurrent capecitabine during long-course chemoradiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision. The planned sample size was 128 participants. Enrollment was discontinued after an interim review after 76 participants had been randomized; long-term follow-up of enrolled participants is ongoing.

Conditions

Rectal Cancer

Keywords

neoadjuvant; rectal cancer; chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• pCR

  Proportion of participants achieving ypT0N0, defined as absence of viable tumor cells in the resected primary tumor and regional lymph nodes after neoadjuvant treatment.

  At total mesorectal excision after completion of neoadjuvant therapy, up to approximately 6 months after randomization

Secondary Outcomes (9)

• Surgical Difficulty

  Time Frame: Perioperative through 30 days after surgery

• Clinical Complete Response (cCR) Rate

  At preoperative restaging after completion of neoadjuvant therapy, before planned surgery

• 3-year overal survival rate

  3 years

• 5-year overal survival rate

  5 years

• 3-year disease free survival rate

  3 years

Study Arms (2)

Online ART With Sequential Boost

EXPERIMENTAL

Participants received online adaptive radiotherapy using MR- or CBCT-guided workflows. A sequential boost of either 9 Gy in 3 fractions or 10 Gy in 2 fractions was delivered to the primary rectal tumor (GTVp) and clinically involved lymph nodes (GTVn), followed by continued online ART to 50 Gy in 25 fractions to the pelvic clinical target volume. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.

Radiation: Online Adaptive Radiotherapy With Sequential Boost; Drug: Capecitabine; Drug: CAPEOX; Procedure: Total Mesorectal Excision

Conventional Non-Adaptive IMRT

ACTIVE COMPARATOR

Participants received conventional non-adaptive intensity-modulated radiotherapy to the pelvic clinical target volume at 50 Gy in 25 fractions without dose escalation. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.

Radiation: Conventional Non-Adaptive IMRT; Drug: Capecitabine; Drug: CAPEOX; Procedure: Total Mesorectal Excision

Interventions

Online Adaptive Radiotherapy With Sequential Boost RADIATION

MR- or CBCT-guided online adaptive radiotherapy with daily imaging, target and organ-at-risk review, and plan reoptimization. A sequential boost of 9 Gy in 3 fractions or 10 Gy in 2 fractions is delivered to GTVp and GTVn, followed by 50 Gy in 25 fractions to the pelvic CTV.

Online ART With Sequential Boost

Conventional Non-Adaptive IMRT RADIATION

Conventional non-adaptive intensity-modulated radiotherapy to the pelvic CTV at 50 Gy in 25 fractions without dose escalation.

Conventional Non-Adaptive IMRT

Capecitabine DRUG

Capecitabine 825 mg/m² orally twice daily during long-course chemoradiotherapy.

Conventional Non-Adaptive IMRT; Online ART With Sequential Boost

CAPEOX DRUG

Consolidation chemotherapy consisting of capecitabine 1000 mg/m² orally twice daily on days 1-14 plus oxaliplatin 130 mg/m² intravenously on day 1 every 3 weeks for 3-4 cycles after chemoradiotherapy.

Conventional Non-Adaptive IMRT; Online ART With Sequential Boost

Total Mesorectal Excision PROCEDURE

Total mesorectal excision planned after completion of neoadjuvant treatment according to standard surgical principles.

Conventional Non-Adaptive IMRT; Online ART With Sequential Boost

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older.
• ECOG performance status of 0 or 1.
• Histologically confirmed rectal adenocarcinoma.
• Primary tumor located within 10 cm of the anal verge by pelvic MRI and/or rigid sigmoidoscopy.
• Clinically involved regional lymph nodes (cN1-2) according to the AJCC 8th edition.
• At least one additional high-risk feature: cT4 disease, cN2 disease, extramural vascular invasion, mesorectal fascia involvement, lateral pelvic lymph-node involvement, tumor deposits, or low rectal cancer (≤5 cm from the anal verge).
• Baseline locoregional staging with contrast-enhanced pelvic MRI and chest/abdominal imaging excluding distant metastases.
• Treatment-naïve with respect to systemic therapy and pelvic radiotherapy for the index rectal cancer and suitable for total mesorectal excision.
• Adequate organ function and no medical contraindication to chemoradiotherapy.
• Written informed consent before study-specific procedures.

You may not qualify if:

• Prior pelvic radiotherapy.
• Prior rectal surgery for the index cancer, including local excision or transanal procedures.
• Radiologically or pathologically confirmed distant metastasis.
• Locally recurrent rectal cancer.
• Active inflammatory bowel disease.
• History of another primary malignancy within the preceding 5 years, except adequately treated non-melanoma skin cancer or carcinoma in situ.
• Pregnancy or lactation.
• Severe or uncontrolled medical condition contraindicating chemoradiotherapy or surgery.
• Clinically significant hypersensitivity to protocol systemic therapy that precludes treatment.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Department of Radiation Oncology, Shandong Cancer Hospital and Institute

Jinan, Shandong, 0531, China

Location

Related Publications (10)

• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12.

  PMID: 33433946 RESULT

• Gollins S, Sebag-Montefiore D. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer. Clin Oncol (R Coll Radiol). 2016 Feb;28(2):146-151. doi: 10.1016/j.clon.2015.11.003. Epub 2015 Nov 29.

  PMID: 26645661 RESULT

• van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Epub 2011 May 17.

  PMID: 21596621 RESULT

• Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, Meunier B, Mehrdad J, Cotte E, Desrame J, Karoui M, Benoist S, Kirzin S, Berger A, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Meurette G, Lupinacci R, Goasgen N, Parc Y, Simon T, Tiret E. Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol. 2016 Nov 1;34(31):3773-3780. doi: 10.1200/JCO.2016.67.6049.

  PMID: 27432930 RESULT

• Fokas E, Schlenska-Lange A, Polat B, Klautke G, Grabenbauer GG, Fietkau R, Kuhnt T, Staib L, Brunner T, Grosu AL, Kirste S, Jacobasch L, Allgauer M, Flentje M, Germer CT, Grutzmann R, Hildebrandt G, Schwarzbach M, Bechstein WO, Sulberg H, Friede T, Gaedcke J, Ghadimi M, Hofheinz RD, Rodel C; German Rectal Cancer Study Group. Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer: Long-term Results of the CAO/ARO/AIO-12 Randomized Clinical Trial. JAMA Oncol. 2022 Jan 1;8(1):e215445. doi: 10.1001/jamaoncol.2021.5445. Epub 2022 Jan 20.

  PMID: 34792531 RESULT

• Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C, Safont MJ, Salud A, Vera R, Massuti B, Escudero P, Alonso V, Bosch C, Martin M, Minsky BD. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trialdagger. Ann Oncol. 2015 Aug;26(8):1722-8. doi: 10.1093/annonc/mdv223. Epub 2015 May 8.

  PMID: 25957330 RESULT

• Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA. 2000 Aug 23-30;284(8):1008-15. doi: 10.1001/jama.284.8.1008.

  PMID: 10944647 RESULT

• Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. doi: 10.1200/JCO.2012.42.9597. Epub 2012 Sep 24.

  PMID: 23008301 RESULT

• Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. doi: 10.1016/S1470-2045(15)00004-2. Epub 2015 Jul 14.

  PMID: 26187751 RESULT

• Wang H, Zhang X, Leng B, Zhu K, Jiang S, Feng R, Dou X, Shi F, Xu L, Yue J. Efficacy and safety of MR-guided adaptive simultaneous integrated boost radiotherapy to primary lesions and positive lymph nodes in the neoadjuvant treatment of locally advanced rectal cancer: a randomized controlled phase III trial. Radiat Oncol. 2024 Sep 12;19(1):118. doi: 10.1186/s13014-024-02506-6.

  PMID: 39267085 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine

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)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jinbo Yue, Doctor

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shandong Cancer Hospital and Institute

Study Record Dates

• First Submitted: January 28, 2024
• First Posted: February 7, 2024
• Study Start: December 1, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)