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

NCT06246344 | Suspended

• 1 other identifier: SDZLEC2023-390-01
• Study Type: observational
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, controlled phase III trial to evaluate the efficacy and safety of adaptive boost radiotherapy to the primary lesions and positive lymph nodes based on MR or CBCT or FBCT-guided adaptive radiotherapy in the neoadjuvant treatment of locally advanced rectal cancer.

Conditions

Rectal Cancer

Keywords

neoadjuvant; rectal cancer; chemoradiotherapy

Outcome Measures

Primary Outcomes (2)

• pCR

  primary tumor achieved pathological complete response

  1 year

• surgical difficulty

  The difficulty score of a surgery is calculated through a comprehensive assessment of the following indicators: surgical blood loss, surgical blood loss, pelvic fibrosis, pelvic fibrosis, degree of edema, number of anastomotic fistulas, and number of urinary dysfunctions.

  2 years

Secondary Outcomes (9)

• cCR

  2 years

• 3-year overal survival rate

  3 years

• 5-year overal survival rate

  5 years

• 3-year disease free suvival rate

  3 years

• 5-year disease free suvival rate

  5 years

Study Arms (2)

Non-ART + non-boost

Radiotherapy: The pelvic lymph node drainage area (CTV) is targeted with a dose of 45-50 Gy delivered in 25 fractions. Concurrent Chemotherapy: During radiotherapy, concurrent administration of capecitabine at a dose of 825 mg/m2, twice daily. Consolidation Chemotherapy Phase: On Day 1, two cycles of the CAPEOX regimen are administered (capecitabine 1.0 g/m2 po bid d1-14 + oxaliplatin 130 mg/m2, q3w). Initiated 7-10 days after completion of LCCRT. Surgical Phase: Commencing on Day 1, the patient undergoes Total Mesorectal Excision (TME) following consolidation chemotherapy.

Radiation: Long course non-ART radiotherapy; Drug: Concurrent chemotherapy; Drug: Consolidation Chemotherapy; Procedure: Total mesorectal excision (TME) surgery

ART + Boost

ART Option 1 (SIB): GTVp+GTVn: A total dose of 60-65 Gy delivered in 25 fractions using a simultaneous integrated boost approach. CTV: A total dose of 45-50 Gy delivered in 25 fractions. ART Option 2 (SB): GTVp+GTVn: An initial hypofractionated boost with a total dose of either 9-12 Gy delivered in 3 fractions or 10 Gy delivered in 2 fractions. Concurrent Chemotherapy: During radiotherapy, concurrent administration of capecitabine at a dose of 825 mg/m2, twice daily. Consolidation Chemotherapy Phase: On Day 1, two cycles of the CAPEOX regimen are administered (capecitabine 1.0 g/m2 po bid d1-14 + oxaliplatin 130 mg/m2, q3w). Initiated 7-10 days after completion of LCCRT. Surgical Phase: Commencing on Day 1, the patient undergoes Total Mesorectal Excision (TME) following consolidation chemotherapy.

Radiation: Adaptive Boost Radiotherapy; Drug: Concurrent chemotherapy; Drug: Consolidation Chemotherapy; Procedure: Total mesorectal excision (TME) surgery

Interventions

Adaptive Boost Radiotherapy RADIATION

The choice of adaptive protocol and delivery system is based on individual tumor characteristics, patient anatomy and institutional capabilities. This approach provides flexibility in treatment planning while adhering to evidence-based dose constraints. Adaptive radiotherapy is delivered using one of the following advanced platforms: the Elekta Unity MRI Linac (MR-guided) or Varian Ethos (CBCT-guided), or the United Imaging uRT-linac 506c (FBCT-guided). ART Option 1 (simultaneous integrated boost, SIB): GTVp+GTVn: A total dose of 60-65 Gy delivered in 25 fractions using a simultaneous integrated boost approach. CTV: A total dose of 45-50 Gy delivered in 25 fractions. ART Option 2 (sequential boost, SB) GTVp+GTVn: An initial hypofractionated boost with a total dose of either 9-12 Gy delivered in 3 fractions or 10 Gy delivered in 2 fractions. CTV: Followed by standard fractionation delivering 45-50 Gy in 25 fractions.

Also known as: ART-boost

ART + Boost

Long course non-ART radiotherapy RADIATION

Conventional long-course radiotherapy administered in a non-adaptive manner without dose escalation. Treatment will be targeted to the pelvic lymphatic drainage region only. A total dose of 45-50 Gy will be delivered in 25 fractions over the course of treatment.

Also known as: non-ART + non-boost

Non-ART + non-boost

Concurrent chemotherapy DRUG

Capecitabine (825 mg/m2, po, twice daily)

ART + Boost; Non-ART + non-boost

Consolidation Chemotherapy DRUG

Following the completion of concurrent chemoradiotherapy, consolidation chemotherapy will commence 7 to 10 days later. Patients will receive two cycles of the CAPEOX regimen. Each cycle comprises: Capecitabine: 1.0 g/m² administered orally twice daily on days 1 through 14, and Oxaliplatin: 130 mg/m² administered intravenously on day 1.

ART + Boost; Non-ART + non-boost

Total mesorectal excision (TME) surgery PROCEDURE

Total mesorectal excision surgery

ART + Boost; Non-ART + non-boost

Eligibility Criteria

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

Study Population

locally advanced rectal cancer

You may qualify if:

• Histopathologically confirmed rectal adenocarcinoma.
• Tumor located ≤10cm from the anal verge.
• Age ≥18 years.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.
• Primary treatment-naive tumor confirmed by endorectal ultrasound (ERUS) or -
• Magnetic resonance imaging (MRI) as cT3-4/N+ according to the 8th edition of AJCC staging.
• Ability to provide tissue and blood samples for translational research.
• Anticipated survival of ≥6 months.
• Normal major organ function (within 14 days prior to enrollment) and suitability for receiving chemoradiotherapy.

You may not qualify if:

• History of prior chemotherapy, radiotherapy, or surgical treatment for rectal cancer, including transanal tumor resection.
• Locally recurrent rectal cancer.
• History of familial adenomatous polyposis.
• Active Crohn's disease or ulcerative colitis.
• Allergy or hypersensitivity history to 5-fluorouracil (fluorouracil) and/or oxaliplatin.
• History of difficulty or inability to take or absorb oral medications.
• Diagnosis of malignancy other than rectal cancer within the past 5 years (excluding completely cured basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma treated with radical resection).
• Confirmed distant metastasis, i.e., cM1, through imaging or biopsy.
• History of pelvic radiotherapy.
• Pregnant or lactating women.
• Presence of any severe or uncontrollable systemic illness.

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

Biospecimen

Retention: SAMPLES WITH DNA

Collecting surgical pathology specimens, fecal samples, and blood from patients.

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Consolidation Chemotherapy; Surgical Procedures, Operative

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

• Jinbo Yue, Doctor

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• 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, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)