pMMR/MSS Locally Advanced Rectal CancerPhase 2NCT07005570
Short-course Radiotherapy Followed by Sequential Chemotherapy With or Without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer （SPARK）
A Phase 2 study testing Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumab and Short-course radiotherapy followed by sequential chemotherapy in people with pMMR/MSS Locally Advanced Rectal Cancer, run by Dechang Diao at 1 site in China.
Trial summary
Safety and efficacy of Short-Course Radiotherapy Followed by Sequential Chemotherapy with or without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- pMMR/MSS Locally Advanced Rectal Cancer
- What is being tested?
- Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumab and Short-course radiotherapy followed by sequential chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2025to 1 Dec 2027
- 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
- Voluntarily signed written informed consent form.
- Age ≥18 and ≤75 years at enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Life expectancy >2 years.
- Histologically confirmed rectal adenocarcinoma.
- Tumor biopsy demonstrating pMMR (all four mismatch repair proteins-MSH1, MSH2, MSH6, and PMS2-positive by immunohistochemistry) or genetic testing confirming MSS (microsatellite stable).
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- Clinical stage II-III rectal cancer (cT3-4NanyM0 or cTxN+M0) per AJCC 8th Edition TNM staging, assessed via high-resolution MRI ± endoscopic ultrasound/transrectal Doppler ultrasound. Tumor must be ≤12 cm from the anal verge by MRI.
- Pre-enrollment surgical evaluation by an attending surgeon confirming eligibility for curative-intent R0 resection.
- No prior systemic or local anti-cancer therapy for rectal cancer (radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy).
- Willingness to provide tumor tissue (archival or fresh biopsy) and peripheral blood samples for biomarker analysis during screening and study procedures.
- Adequate organ function.
- For women of childbearing potential (WOCBP):Negative urine or serum pregnancy test within 3 days prior to treatment (serum test required if urine result is inconclusive).Agreement to use highly effective contraception (e.g., intrauterine device, hormonal implants) from screening until 120 days after last study treatment. Periodic abstinence and calendar-based methods are prohibited.
- The subject is willing and able to comply with scheduled visits, treatment regimens, laboratory tests, and other study requirements as outlined in the protocol.
Who cannot join
- Suspected metastatic lesions or locally advanced unresectable disease regardless of stage.
- History of other malignancies within 5 years prior to enrollment, except those cured by local therapy (e.g., basal/squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the breast).
- Concurrent participation in another interventional clinical trial (observational or non-interventional studies allowed).
- Acute complications requiring emergency surgery (e.g., bowel obstruction, perforation, hemorrhage).
- Multiple primary rectal cancers.
- Prior pelvic/abdominal radiotherapy.
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- Conditions impairing oral drug absorption (e.g., dysphagia, malabsorption syndrome).
- Prior systemic/local anti-tumor therapy for locally advanced rectal cancer (surgery, chemotherapy, radiotherapy, immunotherapy [checkpoint inhibitors/agonists, cell therapy], biologics, or targeted agents).
- Non-specific immunomodulators (e.g., interleukins, interferons) within 2 weeks or anti-tumor herbal medicines within 1 week prior to treatment.
- Active autoimmune disease requiring systemic immunosuppression (e.g., corticosteroids >10 mg/day prednisone equivalent) within 2 years (hormone replacement allowed).
- History of non-infectious pneumonitis or interstitial lung disease requiring steroids.
- Bleeding diathesis/coagulopathy or chronic anticoagulation (e.g., CHADS2 score ≥2 for atrial fibrillation).
- Uncontrolled comorbidities (e.g., decompensated cirrhosis, nephrotic syndrome, peptic ulcers) or psychiatric disorders affecting consent/study compliance.
- Cardiac history:Myocarditis/cardiomyopathy/malignant arrhythmias.Unstable angina/CHF within 12 months.Arterial thromboembolism within 6 months (e.g., stroke, TIA).Grade ≥3 venous thromboembolism (CTCAE v5.0).Uncontrolled hypertension (SBP ≥160 mmHg/DBP ≥100 mmHg).
- Active inflammatory bowel disease (Crohn's/ulcerative colitis) or chronic diarrhea.
- 16Active severe infection requiring hospitalization/systemic antibiotics within 4 weeks (excluding HBV/HCV antivirals).
- 17.Major surgery/trauma within 30 days or minor procedures within 3 days (excluding PICC placement).
- 18.Immunodeficiency (HIV-positive, chronic immunosuppressants). 19.Active tuberculosis (confirmed by sputum/X-ray) or syphilis. 20.Prior allogeneic organ/stem cell transplantation. 21.Active hepatitis:HBV: HBsAg+ with HBV-DNA >1000 copies/mL (200 IU/mL) without antiviral therapy.HCV: Anti-HCV+ with detectable HCV-RNA.
- 22.Live vaccines within 30 days or planned during study. 23.Hypersensitivity to study drugs/monoclonal antibodies. 24.Substance abuse or psychiatric disorders compromising compliance. 25.Pregnancy/lactation. 26.Conditions confounding efficacy/safety assessments or limiting survival evaluation (e.g., leukemoid reaction [WBC >20×10⁹/L], cachexia [>10% weight loss in 3 months], BMI ≤18).
- 27.Other conditions deemed inappropriate by investigators.
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
Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 610655
Dechang Diao, 13416119782, diaodechang@163.com
About this study
Official title: Short-Course Radiotherapy Followed by Sequential Chemotherapy Combined With PD-1 Monoclonal Antibody and Bevacizumab Versus Short-Course Radiotherapy Followed by Sequential Chemotherapy as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer
Safety and efficacy of Short-Course Radiotherapy Followed by Sequential Chemotherapy with or without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer.
Complete Response (CR) Rate of Short-Course Radiotherapy Followed by Sequential Chemotherapy with or without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer.
- Conditions
- pMMR/MSS Locally Advanced Rectal Cancer
- Being tested
- Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumab, Short-course radiotherapy followed by sequential chemotherapy
- Keywords
- PD-1 monoclonal antibody, VEGF monoclonal antibody, total neoadjuvant therapy (TNT), pMMR/MSS locally advanced rectal cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumabOther
Short-course radiotherapy → PD-1 monoclonal antibody and bevacizumab combined with CAPOX regimen chemotherapy (4 cycles) → PD-1 monoclonal antibody combined with CAPOX regimen chemotherapy (2 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine.
Short-course radiotherapy followed by sequential chemotherapyOther
Short-course radiotherapy → CAPOX regimen chemotherapy (6 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Short-course radiotherapy → CAPOX regimen chemotherapy (6 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine. Receives: Other: Short-course radiotherapy followed by sequential chemotherapy |
| Experimental group | Experimental | Short-course radiotherapy → PD-1 monoclonal antibody and bevacizumab combined with CAPOX regimen chemotherapy (4 cycles) → PD-1 monoclonal antibody combined with CAPOX regimen chemotherapy (2 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine. Receives: Other: Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response (CR) Rate
Defined as the proportion of subjects achieving pathological complete response (pCR) or clinical complete response (cCR) following neoadjuvant therapy. pCR is characterized by the absence of residual tumor in the resected primary tumor site and lymph nodes; cCR is defined as achieving ycT0N0 status according to the 2024 CWWD criteria.
Measured: 2-4week
Adverse events
Incidence and severity of adverse events according to CTCAE v5.0.
Measured: 2-4week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2025
- Study start1 May 2025
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for pMMR/MSS Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- 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
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dechang Diao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dechang Diao, Sixth Affiliated Hospital, Sun Yat-sen University
- Investigators
- Dechang Diao, Dr, Study director, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07005570
- Sponsor's protocol ID
- 2025ZSLYEC-288
- Status last verified
- Jan 2026
- First submitted
- 10 May 2025
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-Course Radiotherapy Followed by Sequential Chemotherapy Combined With PD-1 Monoclonal Antibody and Bevacizumab Versus Short-Course Radiotherapy Followed by Sequential Chemotherapy as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT07005570
- Acronym / sponsor ID
- 2025ZSLYEC-288
- Conditions
- pMMR/MSS Locally Advanced Rectal Cancer
- Keywords
- PD-1 monoclonal antibody, VEGF monoclonal antibody, total neoadjuvant therapy (TNT), pMMR/MSS locally advanced rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- Dechang DiaoUniversity, hospital or other
- Study start
- 1 May 2025 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 5 Jun 2025 (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.
Safety and efficacy of Short-Course Radiotherapy Followed by Sequential Chemotherapy with or without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer.
Complete Response (CR) Rate of Short-Course Radiotherapy Followed by Sequential Chemotherapy with or without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in 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 |
|---|---|---|
| Control group | Active comparator | Other: Short-course radiotherapy followed by sequential chemotherapyShort-course radiotherapy → CAPOX regimen chemotherapy (6 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine. |
| Experimental group | Experimental | Other: Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumabShort-course radiotherapy → PD-1 monoclonal antibody and bevacizumab combined with CAPOX regimen chemotherapy (4 cycles) → PD-1 monoclonal antibody combined with CAPOX regimen chemotherapy (2 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Voluntarily signed written informed consent form.
- Age ≥18 and ≤75 years at enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Life expectancy >2 years.
- Histologically confirmed rectal adenocarcinoma.
Key exclusion criteria (20 listed)
- Suspected metastatic lesions or locally advanced unresectable disease regardless of stage.
- History of other malignancies within 5 years prior to enrollment, except those cured by local therapy (e.g., basal/squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the breast).
- Concurrent participation in another interventional clinical trial (observational or non-interventional studies allowed).
- Acute complications requiring emergency surgery (e.g., bowel obstruction, perforation, hemorrhage).
- Multiple primary rectal cancers.
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 |
|---|---|---|
| Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumabShort-course radiotherapy → PD-1 monoclonal antibody and bevacizumab combined with CAPOX regimen chemotherapy (4 cycles) → PD-1 monoclonal antibody combined with CAPOX regimen chemotherapy (2 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine. | Other | Experimental group |
| Short-course radiotherapy followed by sequential chemotherapyShort-course radiotherapy → CAPOX regimen chemotherapy (6 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine. | Other | Control group |
Primary outcome
Complete Response (CR) Rate
Time frame: 2-4week
Defined as the proportion of subjects achieving pathological complete response (pCR) or clinical complete response (cCR) following neoadjuvant therapy. pCR is characterized by the absence of residual tumor in the resected primary tumor site and lymph nodes; cCR is defined as achieving ycT0N0 status according to the 2024 CWWD criteria.
Adverse events
Time frame: 2-4week
Incidence and severity of adverse events according to CTCAE v5.0.
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 21 Jan 2026.
- Individual participant dataSharing planned: No
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Locally Advanced Rectal Cancer (LARC)
Not yet recruitingPhase 2/3
Neoadjuvant Chemoradiotherapy Plus PD-1 Blockade ± CTLA-4 Blockade for High-Risk Locally Advanced Rectal Cancer (pMMR/MSS): A National Multicenter, Prospective, Randomized Controlled Trial
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Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX for pMMR Locally Advanced Rectal Cancer
Colorectal Cancer (CRC)
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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.
Dechang Diao, Dr study director
Sixth Affiliated Hospital, Sun Yat-sen University
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 Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumab and Short-course radiotherapy followed by sequential chemotherapy in people with pMMR/MSS Locally Advanced Rectal Cancer, run by Dechang Diao 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 13 inclusion and 20 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 21 Jan 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 Dechang Diao, Dr (13416119782, diaodch3@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response (CR) Rate (time frame: 2-4week). The study lists 2 primary outcomes in all. 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 21 Jan 2026.