Colorectal Cancer (CRC)Phase 2NCT07448142
Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX for pMMR Locally Advanced Rectal Cancer
A Phase 2 study testing Low-dose radiotherapy, Pucotenlimab and CAPEOX/XELOX in people with Colorectal Cancer (CRC), run by Sun Yat-sen University at 1 site in China.
Trial summary
This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer (CRC)
- What is being tested?
- Low-dose radiotherapy, Pucotenlimab and CAPEOX/XELOX
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 15 Mar 2026to 1 Sep 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent provided prior to any study-specific procedures.
- Age 18 to 75 years at the time of enrollment.
- Histologically confirmed rectal adenocarcinoma.
- Tumor located within 10 cm from the anal verge, as assessed by endoscopy or imaging.
- Locally advanced disease, defined as clinical stage T2N+ or T3-T4a (any N) based on pelvic magnetic resonance imaging (MRI).
- Proficient mismatch repair (pMMR) or microsatellite-stable (MSS) tumor status confirmed by immunohistochemistry or molecular testing.
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- No evidence of distant metastasis on preoperative imaging, including chest, abdominal, and pelvic computed tomography (CT).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Adequate organ function as defined by:
- Absolute neutrophil count ≥1.5 × 10⁹/L
- Platelet count ≥100 × 10⁹/L
- Hemoglobin ≥90 g/L
- Total bilirubin ≤1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
- Creatinine clearance ≥50 mL/min
- Thyroid-stimulating hormone (TSH) within normal limits
- Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for a protocol-defined period after the last dose.
- Men with partners of childbearing potential must agree to use effective contraception during the study and for a protocol-defined period after the last dose.
Who cannot join
- Clinical T4b disease, defined as tumor invasion into adjacent organs or structures on baseline imaging.
- Evidence of distant metastasis outside the pelvis.
- Prior pelvic or abdominal radiotherapy.
- Prior treatment with immune checkpoint inhibitors or other systemic anticancer therapy for rectal cancer.
- Active or history of autoimmune disease requiring systemic treatment, except for conditions considered low risk for recurrence (e.g., vitiligo, resolved childhood asthma).
- Ongoing use of systemic immunosuppressive therapy, including corticosteroids equivalent to >10 mg/day of prednisone, within 2 weeks prior to enrollment.
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- Known human immunodeficiency virus (HIV) infection.
- Active hepatitis B virus infection with positive hepatitis B surface antigen and high viral load, or hepatitis C virus infection requiring treatment.
- Uncontrolled active infection or other serious medical condition that, in the investigator's judgment, would compromise patient safety or study compliance.
- History of another malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies with negligible risk of recurrence.
- Known hypersensitivity or allergy to pucotenlimab, oxaliplatin, capecitabine, or any of their excipients.
- Pregnant or breastfeeding women.
- Any condition that, in the investigator's opinion, makes the participant unsuitable for study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651
Guangzhou, Guanggong, 510060
Wu Jiang, +86-15989120166, jiangwu@sysucc.org.cn
Pei-Rong Ding
About this study
Official title: A Randomized, Two-Arm, Open-Label Phase II Trial of Low-Dose Radiotherapy Sensitization Combined With Pucotenlimab and CAPEOX as Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Adenocarcinoma
This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Tumor response will be assessed after two cycles using endoscopy and pelvic magnetic resonance imaging (MRI). Participants with non-progressive disease, defined as partial response (PR) or stable disease (SD), will receive no further low-dose radiotherapy and will continue pucotenlimab plus CAPEOX for cycles 3 and 4. Participants with local progressive disease, defined as enlargement of the rectal tumor, will receive salvage chemoradiotherapy according to the center's standard operating procedures. Participants who develop distant metastases will receive further treatment determined by a multidisciplinary team (MDT). After four cycles, participants who achieve a clinical complete response (cCR) may enter a watch-and-wait strategy. Participants without cCR and without progressive disease will undergo radical surgery according to total mesorectal excision (TME) principles. Participants with progressive disease will receive individualized treatment determined by the MDT.
Read the detailed description
Rectal cancer remains a major global health burden, with a higher risk of local recurrence and worse prognosis compared with colon cancer. The introduction of total mesorectal excision (TME) has substantially reduced local recurrence rates, and the incorporation of peri-operative radiotherapy and chemotherapy has further improved oncologic outcomes. Current National Comprehensive Cancer Network (NCCN) guidelines recommend pre-operative chemoradiotherapy followed by radical surgery for patients with stage II-III locally advanced rectal cancer.In recent years, total neoadjuvant therapy (TNT) has emerged as an optimized treatment paradigm, increasing pathologic complete response (pCR) rates to approximately 20-40%, and even higher when combined with immunotherapy. For patients achieving a clinical complete response (cCR) after neoadjuvant therapy, a non-operative "watch-and-wait" strategy has been shown to be safe and effective, allowing organ preservation without compromising long-term oncologic outcomes.However, most patients with proficient mismatch repair (pMMR) or microsatellite-stable (MSS) rectal cancer derive limited benefit from immune checkpoint blockade alone. Preclinical and clinical evidence suggests that radiotherapy, particularly low-dose radiotherapy (LDRT), may enhance antitumor immune responses by modulating the tumor microenvironment and promoting immune sensitization. Whether different low-dose radiotherapy regimens can differentially enhance the efficacy of immunotherapy combined with chemotherapy in pMMR/MSS locally advanced rectal cancer remains unknown.To address this question, the present study is designed as a prospective, open-label, randomized, parallel-group phase II clinical trial evaluating a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX chemotherapy as neoadjuvant treatment.Eligible participants with pMMR/MSS locally advanced rectal adenocarcinoma will be randomized in a 1:1 ratio to receive either 2 Gy or 5 Gy low-dose radiotherapy. On the day following radiotherapy, all participants will initiate systemic treatment with pucotenlimab 200 mg administered intravenously every 3 weeks (Q3W) on Day 2, in combination with CAPEOX chemotherapy in 21-day cycles. An early response assessment will be performed after two cycles of neoadjuvant treatment using endoscopy and pelvic MRI. Participants with PR or SD will discontinue any further low-dose radiotherapy and will complete the remaining two cycles of pucotenlimab plus CAPEOX. Participants with local progressive disease, defined as enlargement of the rectal lesion, will receive salvage chemoradiotherapy, with the treatment regimen and implementation procedures following the center's standardized SOP. Participants with distant metastases will undergo MDT review to determine subsequent treatment based on disease status, treatment response, and tolerability. A further response assessment will be performed after four cycles. Participants achieving cCR may enter watch-and-wait surveillance. Participants who do not achieve cCR and have no progressive disease will undergo standard TME surgery. Participants with progressive disease will undergo MDT review for individualized management. The primary objective of this study is to compare the complete response rate, defined as the sum of clinical complete response and pathological complete response, between the two low-dose radiotherapy regimens. Secondary objectives include long-term disease control, survival outcomes, surgical quality metrics, postoperative morbidity, stoma rates, and patient-reported quality of life. This study aims to determine whether optimization of low-dose radiotherapy can enhance immune-chemotherapy efficacy and increase organ preservation opportunities in patients with pMMR/MSS locally advanced rectal cancer.
- Conditions
- Colorectal Cancer (CRC)
- Being tested
- Low-dose radiotherapy, Pucotenlimab, CAPEOX/XELOX
- Keywords
- Colorectal cancer, Neoadjuvant therapy, Low-dose radiotherapy, Immunotherapy, Pucotenlimab, CAPEOX, Total neoadjuvant therapy, Organ preservation, Complete Response Rate, Disease-free survival, Overall survival
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose radiotherapyRadiation
Low-dose radiotherapy is delivered to the primary rectal tumor and regional lymphatic drainage areas using IMRT or 3D-CRT. Participants receive one fraction at the start of each of the first two 21-day cycles: 2 Gy per fraction in Arm A (planned total dose 4 Gy) or 5 Gy per fraction in Arm B (planned total dose 10 Gy), excluding any salvage radiotherapy. No further low-dose radiotherapy is administered during cycles 3 and 4 in participants with PR or SD at the two-cycle assessment. Local progressive disease is managed with salvage chemoradiotherapy according to the center's SOP.
PucotenlimabDrug
Pucotenlimab is a programmed cell death protein 1 (PD-1) monoclonal antibody. It is administered at a fixed dose of 200 mg by intravenous infusion on Day 2 of each 21-day cycle, every 3 weeks (Q3W), during the neoadjuvant treatment phase.
CAPEOX/XELOXDrug
CAPEOX chemotherapy consists of oxaliplatin 130 mg/m² administered intravenously on Day 1 and capecitabine 1000-1250 mg/m² administered orally twice daily on Days 1-14 of each 21-day cycle during neoadjuvant therapy.
| Study group | Role | What they receive |
|---|---|---|
| 2 Gy LDRT + Pucotenlimab + CAPEOX | Experimental | Neoadjuvant low-dose radiotherapy (2 Gy) followed by pucotenlimab 200 mg IV Q3W plus CAPEOX chemotherapy.
Participants receive one 2 Gy fraction of low-dose radiotherapy in each of cycles 1 and 2, for a planned total dose of 4 Gy before any salvage treatment, combined with pucotenlimab and CAPEOX in a response-adapted neoadjuvant treatment strategy. Response is assessed after two cycles. Participants with PR or SD complete cycles 3 and 4 with pucotenlimab plus CAPEOX without further low-dose radiotherapy; those with local progression receive salvage chemoradiotherapy according to the center's SOP; and those with distant metastases receive MDT-directed treatment. After four cycles, cCR permits watch-and-wait surveillance, non-cCR without progression leads to standard TME surgery, and progressive disease is managed through MDT review. Receives: Radiation: Low-dose radiotherapy; Drug: Pucotenlimab; Drug: CAPEOX/XELOX |
| 5 Gy LDRT + Pucotenlimab + CAPEOX | Experimental | Neoadjuvant low-dose radiotherapy (5 Gy) followed by pucotenlimab 200 mg IV Q3W plus CAPEOX chemotherapy.
Participants receive one 5 Gy fraction of low-dose radiotherapy in each of cycles 1 and 2, for a planned total dose of 10 Gy before any salvage treatment, combined with pucotenlimab and CAPEOX in a response-adapted neoadjuvant treatment strategy. Response is assessed after two cycles. Participants with PR or SD complete cycles 3 and 4 with pucotenlimab plus CAPEOX without further low-dose radiotherapy; those with local progression receive salvage chemoradiotherapy according to the center's SOP; and those with distant metastases receive MDT-directed treatment. After four cycles, cCR permits watch-and-wait surveillance, non-cCR without progression leads to standard TME surgery, and progressive disease is managed through MDT review. Receives: Radiation: Low-dose radiotherapy; Drug: Pucotenlimab; Drug: CAPEOX/XELOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate (CR)
The Combined CR rate is defined as the percentage of participants achieving either Clinical Complete Response (cCR) or Pathologic Complete Response (pCR). cCR is assessed via pelvic MRI, digital rectal examination (DRE), and endoscopy following the completion of 4 cycles of neoadjuvant therapy (each cycle is 21 days). For patients who do not achieve cCR and subsequently undergo radical surgery (scheduled 2-4 weeks after the last dose of neoadjuvant therapy), pCR is assessed by pathological examination of the resected surgical specimen (Tumor Regression Grading, TRG 0) according to the AJCC/College of American Pathologists (CAP) guidelines. For participants receiving salvage chemoradiotherapy, response assessment and surgery will follow the salvage treatment schedule specified in the protocol and the center's SOP.
Measured: From the start of neoadjuvant therapy until the completion of pre-operative assessment (approximately 12 weeks) and the time of surgery (approximately 14-16 weeks).
Secondary outcomes (7)
3-year Disease-Free Survival (DFS)
Disease-free survival is defined as the time from randomization to the first documented occurrence of tumor recurrence (local or distant) or death from any cause, whichever occurs first.
Measured: Up to 3 years after randomization.
5-year Overall Survival (OS)
Overall survival is defined as the time from randomization to death from any cause.
Measured: Up to 5 years after randomization.
Distant Metastasis Rate
The proportion of participants who develop distant metastasis during follow-up, confirmed by radiologic or pathologic assessment.
Measured: Up to 5 years after randomization.
R0 Resection Rate
The proportion of participants who achieve microscopically margin-negative (R0) resection at the time of surgery.
Measured: At the time of surgery.
Postoperative Surgical Complication Rate
The proportion of participants experiencing postoperative surgical complications, graded according to standard surgical complication criteria.
Measured: Within 30 days after surgery.
Protective Stoma Rate
The proportion of participants who undergo prophylactic diverting stoma creation at the time of surgery.
Measured: At the time of surgery.
Quality of Life (EORTC QLQ-C30)
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), version 3.0.
Measured: From baseline through follow-up (up to 5 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2026
- Study start15 Mar 2026
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Sep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pei-Rong Ding, Sun Yat-sen University
- Investigators
- Pei-Rong Ding, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07448142
- Sponsor's protocol ID
- 2025-FXY-301
- Other IDs
- B2025-700
- Status last verified
- Oct 2026
- First submitted
- 9 Feb 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Two-Arm, Open-Label Phase II Trial of Low-Dose Radiotherapy Sensitization Combined With Pucotenlimab and CAPEOX as Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT07448142
- Acronym / sponsor ID
- 2025-FXY-301
- Conditions
- Colorectal Cancer (CRC)
- Keywords
- Colorectal cancer, Neoadjuvant therapy, Low-dose radiotherapy, Immunotherapy, Pucotenlimab, CAPEOX, Total neoadjuvant therapy, Organ preservation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 15 Mar 2026 (actual)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Sep 2032 (estimated)
- First posted
- 4 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Tumor response will be assessed after two cycles using endoscopy and pelvic magnetic resonance imaging (MRI). Participants with non-progressive disease, defined as partial response (PR) or stable disease (SD), will receive no further low-dose radiotherapy and will continue pucotenlimab plus CAPEOX for cycles 3 and 4. Participants with local progressive disease, defined as enlargement of the rectal tumor, will receive salvage chemoradiotherapy according to the center's standard operating procedures. Participants who develop distant metastases will receive further treatment determined by a multidisciplinary team (MDT). After four cycles, participants who achieve a clinical complete response (cCR) may enter a watch-and-wait strategy. Participants without cCR and without progressive disease will undergo radical surgery according to total mesorectal excision (TME) principles. Participants with progressive disease will receive individualized treatment determined by the MDT.
Detailed description
Rectal cancer remains a major global health burden, with a higher risk of local recurrence and worse prognosis compared with colon cancer. The introduction of total mesorectal excision (TME) has substantially reduced local recurrence rates, and the incorporation of peri-operative radiotherapy and chemotherapy has further improved oncologic outcomes. Current National Comprehensive Cancer Network (NCCN) guidelines recommend pre-operative chemoradiotherapy followed by radical surgery for patients with stage II-III locally advanced rectal cancer.In recent years, total neoadjuvant therapy (TNT) has emerged as an optimized treatment paradigm, increasing pathologic complete response (pCR) rates to approximately 20-40%, and even higher when combined with immunotherapy. For patients achieving a clinical complete response (cCR) after neoadjuvant therapy, a non-operative "watch-and-wait" strategy has been shown to be safe and effective, allowing organ preservation without compromising long-term oncologic outcomes.However, most patients with proficient mismatch repair (pMMR) or microsatellite-stable (MSS) rectal cancer derive limited benefit from immune checkpoint blockade alone. Preclinical and clinical evidence suggests that radiotherapy, particularly low-dose radiotherapy (LDRT), may enhance antitumor immune responses by modulating the tumor microenvironment and promoting immune sensitization. Whether different low-dose radiotherapy regimens can differentially enhance the efficacy of immunotherapy combined with chemotherapy in pMMR/MSS locally advanced rectal cancer remains unknown.To address this question, the present study is designed as a prospective, open-label, randomized, parallel-group phase II clinical trial evaluating a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX chemotherapy as neoadjuvant treatment.Eligible participants with pMMR/MSS locally advanced rectal adenocarcinoma will be randomized in a 1:1 ratio to receive either 2 Gy or 5 Gy low-dose radiotherapy. On the day following radiotherapy, all participants will initiate systemic treatment with pucotenlimab 200 mg administered intravenously every 3 weeks (Q3W) on Day 2, in combination with CAPEOX chemotherapy in 21-day cycles. An early response assessment will be performed after two cycles of neoadjuvant treatment using endoscopy and pelvic MRI. Participants with PR or SD will discontinue any further low-dose radiotherapy and will complete the remaining two cycles of pucotenlimab plus CAPEOX. Participants with local progressive disease, defined as enlargement of the rectal lesion, will receive salvage chemoradiotherapy, with the treatment regimen and implementation procedures following the center's standardized SOP. Participants with distant metastases will undergo MDT review to determine subsequent treatment based on disease status, treatment response, and tolerability. A further response assessment will be performed after four cycles. Participants achieving cCR may enter watch-and-wait surveillance. Participants who do not achieve cCR and have no progressive disease will undergo standard TME surgery. Participants with progressive disease will undergo MDT review for individualized management. The primary objective of this study is to compare the complete response rate, defined as the sum of clinical complete response and pathological complete response, between the two low-dose radiotherapy regimens. Secondary objectives include long-term disease control, survival outcomes, surgical quality metrics, postoperative morbidity, stoma rates, and patient-reported quality of life. This study aims to determine whether optimization of low-dose radiotherapy can enhance immune-chemotherapy efficacy and increase organ preservation opportunities in patients with pMMR/MSS locally advanced rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 Gy LDRT + Pucotenlimab + CAPEOX | Experimental | Radiation: Low-dose radiotherapy, Drug: Pucotenlimab, Drug: CAPEOX/XELOXNeoadjuvant low-dose radiotherapy (2 Gy) followed by pucotenlimab 200 mg IV Q3W plus CAPEOX chemotherapy. Participants receive one 2 Gy fraction of low-dose radiotherapy in each of cycles 1 and 2, for a planned total dose of 4 Gy before any salvage treatment, combined with pucotenlimab and CAPEOX in a response-adapted neoadjuvant treatment strategy. Response is assessed after two cycles. Participants with PR or SD complete cycles 3 and 4 with pucotenlimab plus CAPEOX without further low-dose radiotherapy; those with local progression receive salvage chemoradiotherapy according to the center's SOP; and those with distant metastases receive MDT-directed treatment. After four cycles, cCR permits watch-and-wait surveillance, non-cCR without progression leads to standard TME surgery, and progressive disease is managed through MDT review. |
| 5 Gy LDRT + Pucotenlimab + CAPEOX | Experimental | Radiation: Low-dose radiotherapy, Drug: Pucotenlimab, Drug: CAPEOX/XELOXNeoadjuvant low-dose radiotherapy (5 Gy) followed by pucotenlimab 200 mg IV Q3W plus CAPEOX chemotherapy. Participants receive one 5 Gy fraction of low-dose radiotherapy in each of cycles 1 and 2, for a planned total dose of 10 Gy before any salvage treatment, combined with pucotenlimab and CAPEOX in a response-adapted neoadjuvant treatment strategy. Response is assessed after two cycles. Participants with PR or SD complete cycles 3 and 4 with pucotenlimab plus CAPEOX without further low-dose radiotherapy; those with local progression receive salvage chemoradiotherapy according to the center's SOP; and those with distant metastases receive MDT-directed treatment. After four cycles, cCR permits watch-and-wait surveillance, non-cCR without progression leads to standard TME surgery, and progressive disease is managed through MDT review. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Written informed consent provided prior to any study-specific procedures.
- Age 18 to 75 years at the time of enrollment.
- Histologically confirmed rectal adenocarcinoma.
- Tumor located within 10 cm from the anal verge, as assessed by endoscopy or imaging.
- Locally advanced disease, defined as clinical stage T2N+ or T3-T4a (any N) based on pelvic magnetic resonance imaging (MRI).
Key exclusion criteria (13 listed)
- Clinical T4b disease, defined as tumor invasion into adjacent organs or structures on baseline imaging.
- Evidence of distant metastasis outside the pelvis.
- Prior pelvic or abdominal radiotherapy.
- Prior treatment with immune checkpoint inhibitors or other systemic anticancer therapy for rectal cancer.
- Active or history of autoimmune disease requiring systemic treatment, except for conditions considered low risk for recurrence (e.g., vitiligo, resolved childhood asthma).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-dose radiotherapyLow-dose radiotherapy is delivered to the primary rectal tumor and regional lymphatic drainage areas using IMRT or 3D-CRT. Participants receive one fraction at the start of each of the first two 21-day cycles: 2 Gy per fraction in Arm A (planned total dose 4 Gy) or 5 Gy per fraction in Arm B (planned total dose 10 Gy), excluding any salvage radiotherapy. No further low-dose radiotherapy is administered during cycles 3 and 4 in participants with PR or SD at the two-cycle assessment. Local progressive disease is managed with salvage chemoradiotherapy according to the center's SOP. | Radiation | 2 Gy LDRT + Pucotenlimab + CAPEOX, 5 Gy LDRT + Pucotenlimab + CAPEOX |
| PucotenlimabPucotenlimab is a programmed cell death protein 1 (PD-1) monoclonal antibody. It is administered at a fixed dose of 200 mg by intravenous infusion on Day 2 of each 21-day cycle, every 3 weeks (Q3W), during the neoadjuvant treatment phase. | Drug | 2 Gy LDRT + Pucotenlimab + CAPEOX, 5 Gy LDRT + Pucotenlimab + CAPEOX |
| CAPEOX/XELOXCAPEOX chemotherapy consists of oxaliplatin 130 mg/m² administered intravenously on Day 1 and capecitabine 1000-1250 mg/m² administered orally twice daily on Days 1-14 of each 21-day cycle during neoadjuvant therapy. | Drug | 2 Gy LDRT + Pucotenlimab + CAPEOX, 5 Gy LDRT + Pucotenlimab + CAPEOX |
Primary outcome
Complete Response Rate (CR)
Time frame: From the start of neoadjuvant therapy until the completion of pre-operative assessment (approximately 12 weeks) and the time of surgery (approximately 14-16 weeks).
The Combined CR rate is defined as the percentage of participants achieving either Clinical Complete Response (cCR) or Pathologic Complete Response (pCR). cCR is assessed via pelvic MRI, digital rectal examination (DRE), and endoscopy following the completion of 4 cycles of neoadjuvant therapy (each cycle is 21 days). For patients who do not achieve cCR and subsequently undergo radical surgery (scheduled 2-4 weeks after the last dose of neoadjuvant therapy), pCR is assessed by pathological examination of the resected surgical specimen (Tumor Regression Grading, TRG 0) according to the AJCC/College of American Pathologists (CAP) guidelines. For participants receiving salvage chemoradiotherapy, response assessment and surgery will follow the salvage treatment schedule specified in the protocol and the center's SOP.
7 secondary outcomes
3-year Disease-Free Survival (DFS)
Time frame: Up to 3 years after randomization.
5-year Overall Survival (OS)
Time frame: Up to 5 years after randomization.
Distant Metastasis Rate
Time frame: Up to 5 years after randomization.
R0 Resection Rate
Time frame: At the time of surgery.
Postoperative Surgical Complication Rate
Time frame: Within 30 days after surgery.
Protective Stoma Rate
Time frame: At the time of surgery.
Quality of Life (EORTC QLQ-C30)
Time frame: From baseline through follow-up (up to 5 years).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pei-Rong Ding principal investigator
Sun Yat-Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low-dose radiotherapy, Pucotenlimab and CAPEOX/XELOX in people with Colorectal Cancer (CRC), run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wu Jiang (+86-15989120166, jiangwu@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response Rate (CR) (time frame: From the start of neoadjuvant therapy until the completion of pre-operative assessment (approximately 12 weeks) and the time of surgery (approximately 14-16 weeks).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.