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

April 27, 2026 updated by: Jinbo Yue, Shandong Cancer Hospital and Institute

Efficacy and Safety of Adaptive Boost Radiotherapy to Primary Lesions and Positive Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: A Prospective, Randomized, Controlled, Phase III Trial

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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

Locally advanced rectal cancer (LARC), typically stage II (cT3-4/N0) or stage III (cT1-4/N1-3), requires multimodal treatment. Surgical resection alone is associated with a high rate of local recurrence. Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME), on the other hand, can better control local recurrence in LARC patients. However, the overall pathological complete response (pCR) rate and clinical complete response (cCR) rate are still low, and there is an inconsistency between them, Therefore, the preservation of the anus is still a challenge. Optimizing neoadjuvant treatment strategies, including strategies such as increasing concurrent chemotherapy and increasing the dose of radiotherapy, is essential to improve tumor regression and anal preservation.

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.

Study Type

Observational

Enrollment (Estimated)

128

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shandong
      • Jinan, Shandong, China, 0531
        • Department of Radiation Oncology, Shandong Cancer Hospital and Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

locally advanced rectal cancer

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
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.
Other Names:
  • non-ART + non-boost
Drug: Concurrent chemotherapy
Capecitabine (825 mg/m2, po, twice daily)
Drug: 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.
Procedure: 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.
Drug: Concurrent chemotherapy
Capecitabine (825 mg/m2, po, twice daily)
Drug: 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.
Procedure: Total mesorectal excision (TME) surgery
Total mesorectal excision surgery
Radiation: 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.

Other Names:
  • ART-boost

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pCR
Time Frame: 1 year
primary tumor achieved pathological complete response
1 year
surgical difficulty
Time Frame: 2 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
cCR
Time Frame: 2 years
primary tumor achieved clinical complete response
2 years
3-year overal survival rate
Time Frame: 3 years
The proportion of patients from the commencement of self-diagnosis to the time of death for any reason within 3 years
3 years
5-year overal survival rate
Time Frame: 5 years
The proportion of patients from the commencement of self-diagnosis to the time of death for any reason within 5 years
5 years
3-year disease free suvival rate
Time Frame: 3 years
The proportion of patients from the initiation of surgery to tumor recurrence or death within 3 years
3 years
5-year disease free suvival rate
Time Frame: 5 years
The proportion of patients from the initiation of surgery to tumor recurrence or death within 5 years
5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. Higher scores mean a worse outcome.
3 years
The Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system
Time Frame: 3 years
The Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system for grading of side effects after radiotherapy was proposed, mainly including tenesmus, mucosal loss, sphincter control, stool frequency, pain, bleeding, ulceration, stricture, etc. Higher scores mean a worse outcome.
3 years
Quality of life assessment using the EORTC QLQ-C30 questionnaire
Time Frame: 3 year
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a validated instrument designed to assess quality of life in cancer patients. It comprises 30 items divided into multi-item scales and single-item measures evaluating global health status/quality of life, various functioning domains (physical, role, emotional, cognitive, social), and a range of symptoms. Scores for each scale range from 0 to 100. For the global health status and functioning scales, higher scores indicate a better outcome, while for the symptom scales, higher scores indicate more severe symptoms and thus a worse outcome.
3 year
Quality of life assessment using the EORTC QLQ-CR29 questionnaire
Time Frame: 3 years
The EORTC QLQ-CR29 is a validated colorectal cancer-specific quality of life instrument designed to complement the QLQ-C30 core questionnaire. It consists of 29 items assessing both functional aspects (e.g. body image and sexual functioning) and symptom domains specific to colorectal cancer. Scores for each domain are linearly transformed to a 0-100 scale. For the functional scales, higher scores indicate better quality of life, whereas for the symptom scales, higher scores indicate greater symptom burden and consequently worse outcome.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shandong Cancer Hospital and Institute

Investigators

  • Principal Investigator: Jinbo Yue, Doctor, Shandong Cancer Hospital and Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2023

Primary Completion (Actual)

December 1, 2025

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

January 28, 2024

First Submitted That Met QC Criteria

February 4, 2024

First Posted (Actual)

February 7, 2024

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SDZLEC2023-390-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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