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

September 10, 2026 updated by: Jinbo Yue, Shandong Cancer Hospital and Institute

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The trial was originally designed to evaluate adaptive dose escalation to the primary rectal tumor and clinically involved lymph nodes during neoadjuvant treatment for locally advanced rectal cancer. During trial conduct, the protocol was amended to reflect the treatment strategy implemented in the enrolled cohort. Enrollment was operationally consolidated at the lead center. Online ART was delivered using either MR-guided or CBCT-guided workflows. In the experimental arm, a sequential boost of 9 Gy in 3 fractions or 10 Gy in 2 fractions was delivered to the primary tumor and clinically involved lymph nodes, followed by online ART to 50 Gy in 25 fractions to the pelvic clinical target volume. The control arm received conventional non-adaptive IMRT to 50 Gy in 25 fractions without dose escalation. Both groups received concurrent capecitabine and 3-4 cycles of CAPEOX consolidation chemotherapy.

The planned enrollment was 128 participants. During trial conduct, an interim review was undertaken after 76 participants had been randomized. The interim analysis had not been specified in the original protocol and no formal group-sequential efficacy or futility boundary had been prespecified. Enrollment was subsequently discontinued, while protocol-defined follow-up of enrolled participants continues.

Study Type

Interventional

Enrollment (Estimated)

128

Phase

  • Phase 3

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

Study Population

locally advanced rectal cancer

Description

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.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Online ART With Sequential Boost
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
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.
Drug: Capecitabine
Capecitabine 825 mg/m² orally twice daily during long-course chemoradiotherapy.
Drug: CAPEOX
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.
Procedure: Total Mesorectal Excision
Total mesorectal excision planned after completion of neoadjuvant treatment according to standard surgical principles.
Active Comparator: Conventional Non-Adaptive IMRT
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.
Drug: Capecitabine
Capecitabine 825 mg/m² orally twice daily during long-course chemoradiotherapy.
Drug: CAPEOX
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.
Procedure: Total Mesorectal Excision
Total mesorectal excision planned after completion of neoadjuvant treatment according to standard surgical principles.
Radiation: Conventional Non-Adaptive IMRT
Conventional non-adaptive intensity-modulated radiotherapy to the pelvic CTV at 50 Gy in 25 fractions without dose escalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pCR
Time Frame: At total mesorectal excision after completion of neoadjuvant therapy, up to approximately 6 months after randomization
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Surgical Difficulty
Time Frame: Time Frame: Perioperative through 30 days after surgery
urgical difficulty is assessed using a predefined 8-item composite score incorporating operative time, conversion to laparotomy, non-routine transanal assistance, visible pelvic fibrosis, bowel edema, intraoperative blood loss, postoperative hospital stay, and postoperative complications. The total score ranges from 0 to 12; a score ≥3 defines difficult surgery.
Time Frame: Perioperative through 30 days after surgery
Clinical Complete Response (cCR) Rate
Time Frame: At preoperative restaging after completion of neoadjuvant therapy, before planned surgery
Proportion of participants meeting the protocol-defined criteria for clinical complete response at restaging, based on pelvic MRI, endoscopy, and digital rectal examination, with biopsy when performed. Criteria include no residual tumor or only residual fibrosis on MRI, no suspicious residual lymph nodes, no residual tumor on endoscopy or only a small scar/ulcer, and no palpable residual tumor.
At preoperative restaging after completion of neoadjuvant therapy, before planned surgery
3-year disease free survival rate
Time Frame: 3 years
The proportion of patients from the initiation of surgery to tumor recurrence or death within 3 years
3 years
Treatment-related adverse events
Time Frame: 1 year
Number and proportion of participants experiencing treatment-related adverse events, graded according to CTCAE version 5.0 and protocol-specified radiation morbidity criteria.
1 year
Perioperative complications
Time Frame: From surgery through 30 days after surgery
Incidence of perioperative complications after TME, including wound/incision complications, bleeding, infection, and procedure-specific complications
From surgery through 30 days after surgery
Perineal wound healing after APR
Time Frame: Through 6 months after surgery
Perineal wound-healing outcomes and wound complications among participants undergoing abdominoperineal resection.
Through 6 months after surgery

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, 2030

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)

September 15, 2026

Last Update Submitted That Met QC Criteria

September 10, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SDZLEC2023-390-02

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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