Clinical trial · Interventional
Adaptive Boost Radiotherapy to Primary Lesions and Positive Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer
Online Adaptive Radiotherapy With a Boost to the Primary Tumor and Clinically Involved Lymph Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: A Prospective, Randomized Controlled Trial
NCT06246344CI-TRIAL-00110018active not recruitingPhase 3ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 16, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260916-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Rectal Cancer | Malignant Rectal Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Capecitabine | Drug | Capecitabine | ALIAS |
| CAPEOX | Drug | CAPOX Regimen | ALIAS |
| Conventional Non-Adaptive IMRT | Radiation | — | UNRESOLVED |
| Online Adaptive Radiotherapy With Sequential Boost | Radiation | — | UNRESOLVED |
| Total Mesorectal Excision | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Online ART With Sequential Boost
- description
- 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.
- interventionNames
- Radiation: Online Adaptive Radiotherapy With Sequential Boost
- Drug: Capecitabine
- Drug: CAPEOX
- Procedure: Total Mesorectal Excision
- type
- ACTIVE_COMPARATOR
- label
- Conventional Non-Adaptive IMRT
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
Inclusion Criteria 1. Age 18 years or older. 2. ECOG performance status of 0 or 1. 3. Histologically confirmed rectal adenocarcinoma. 4. Primary tumor located within 10 cm of the anal verge by pelvic MRI and/or rigid sigmoidoscopy. 5. Clinically involved regional lymph nodes (cN1-2) according to the AJCC 8th edition. 6. 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). 7. Baseline locoregional staging with contrast-enhanced pelvic MRI and chest/abdominal imaging excluding distant metastases. 8. Treatment-naïve with respect to systemic therapy and pelvic radiotherapy for the index rectal cancer and suitable for total mesorectal excision. 9. Adequate organ function and no medical contraindication to chemoradiotherapy. 10. Written informed consent before study-specific procedures. Exclusion Criteria 1. Prior pelvic radiotherapy. 2. Prior rectal surgery for the index cancer, including local excision or transanal procedures. 3. Radiologically or pathologically confirmed distant metastasis. 4. Locally recurrent rectal cancer. 5. Active inflammatory bowel disease. 6. History of another primary malignancy within the preceding 5 years, except adequately treated non-melanoma skin cancer or carcinoma in situ. 7. Pregnancy or lactation. 8. Severe or uncontrolled medical condition contraindicating chemoradiotherapy or surgery. 9. Clinically significant hypersensitivity to protocol systemic therapy that precludes treatment.
References
Publications (10)
- RESULTSiegel 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
- RESULTGollins 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
- RESULTvan 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
- RESULTLefevre 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
- RESULTFokas 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