Adaptive Boost Radiotherapy to Primary Lesions and Positive Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer
NCT ID: NCT06246344
Last Updated: 2025-03-12
Study Results
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Basic Information
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RECRUITING
128 participants
OBSERVATIONAL
2023-12-01
2028-12-01
Brief Summary
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Detailed Description
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Radiotherapy is an important treatment for controlling local recurrence and downstaging LARC. A common cause of cancer recurrence in rectal cancer is that tumor cells metastasise nearby positive lymph nodes, such as the lateral pelvic lymph nodes These sites can serve as refuges where the cancer can regroup and either recur at the original site or spread to other areas. Various studies have also investigated the role of radiotherapy dose escalation in promoting tumor regression. Seldom have these studies examined dose escalation to both the primary lesions and positive lymph nodes. One of the major limiting factors is the tradeoff between destruction of the cancer itself and collateral damage to the neighboring healthy tissues. However, recent advances in the field have made great strides in overcoming this obstacle. Adaptive radiation therapy (ART), including magnetic resonance (MR)-guided, cone beam computed tomography (CBCT)-guided, and fan beam computed tomography (FBCT)-guided, allows direct imaging of the target and organs at risk (OAR), combined with optimization of the treatment plan for anatomical changes, to deliver high-quality dose escalation regimens to improve treatment response while protecting OAR such as the bladder, femoral heads, and small bowel.
We hypothesize that by implementing simultaneous integrated boost (SIB) or sequential boost (SB) radiotherapy to both the primary lesions and positive lymph nodes based on ART, we can improve the cCR and pCR rates without increasing surgical difficulty, while maintaining tolerable safety.
Against the above background, this study aims to conduct a multicenter, randomized, controlled phase III trial to evaluate the efficacy and safety of SIB or SB radiotherapy to the primary lesions and positive lymph nodes based on MR or CBCT or FBCT-guided ART in the neoadjuvant treatment of LARC. Eligible patients will be randomized 1:1 into experimental and control groups, both of which will undergo long course concurrent chemoradiotherapy (LCCRT), consolidation chemotherapy and TME surgery. During LCCRT, the experimental group will receive SIB or SB dose escalation based on MR or CBCT or FBCT-guided ART, while the control group will receive conventional dose without ART.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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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.
Long course non-ART radiotherapy
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.
Concurrent chemotherapy
Capecitabine (825 mg/m2, po, twice daily)
Consolidation Chemotherapy
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.
Total mesorectal excision (TME) surgery
Total mesorectal excision 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.
Adaptive Boost Radiotherapy
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.
Concurrent chemotherapy
Capecitabine (825 mg/m2, po, twice daily)
Consolidation Chemotherapy
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.
Total mesorectal excision (TME) surgery
Total mesorectal excision surgery
Interventions
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Adaptive Boost Radiotherapy
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.
Long course non-ART radiotherapy
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.
Concurrent chemotherapy
Capecitabine (825 mg/m2, po, twice daily)
Consolidation Chemotherapy
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.
Total mesorectal excision (TME) surgery
Total mesorectal excision surgery
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
* 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.
18 Years
75 Years
ALL
No
Sponsors
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Shandong Cancer Hospital and Institute
OTHER
Responsible Party
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Jinbo Yue
Shandong Cancer Hospital and Institute
Principal Investigators
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Jinbo Yue, Doctor
Role: PRINCIPAL_INVESTIGATOR
Shandong Cancer Hospital and Institute
Locations
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Department of Radiation Oncology, Shandong Cancer Hospital and Institute
Jinan, Shandong, China
Countries
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Central Contacts
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Facility Contacts
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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SDZLEC2023-390-01
Identifier Type: -
Identifier Source: org_study_id
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