Rectal CancerPhase 2NCT07847229
A Prospective, Biomarker-Stratified Phase 2 Study: β-Hydroxybutyrate as a Predictive Biomarker for Short-Course Radiotherapy Followed by Chemotherapy Plus PD-1 Inhibitor Versus Chemotherapy Alone in Locally Advanced Rectal Cancer
A Phase 2 study testing Short-course radiotherapy, Capecitabine and Oxaliplatin in people with Rectal Cancer and Radiotherapy, run by Tao Zhang at 1 site in China.
Trial summary
This is a prospective, single-arm, biomarker-stratified, multicenter phase 2 clinical trial. All enrolled patients first receive short-course radiotherapy (SCRT), followed by measurement of serum β-hydroxybutyrate (β-HB) levels to calculate the post-radiotherapy elevation rate. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer, Radiotherapy, Immunotherapy
- What is being tested?
- Short-course radiotherapy, Capecitabine and Oxaliplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2026to 30 Apr 2028
- 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
- Patients or their family members agree to participate in the study and sign the informed consent form;
- Age 18-75 years, male or female;
- Histologically confirmed Locally Advanced rectal adenocarcinoma;
- inferior margin ≤ 10 cm from the anal verge;
- ECOG performance status score is 0-1;
- Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc;
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- There was no operative contraindication;
- Laboratory tests were required to meet the following requirements: white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
- Urinary protein < 2+ or 24-hour urinary protein excretion < 1 g at baseline.
Who cannot join
- Patients with non-pMMR LARC；
- Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms;
- Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Tao Zhang contact
China1 site
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430000
About this study
This is a prospective, single-arm, biomarker-stratified, multicenter phase 2 clinical trial. All enrolled patients first receive short-course radiotherapy (SCRT), followed by measurement of serum β-hydroxybutyrate (β-HB) levels to calculate the post-radiotherapy elevation rate. Patients are stratified into an β-HB-positive stratum (elevation significantly) and an β-HB-negative stratum (no elevation), then randomized 1:1 within each stratum to receive either perioperative chemotherapy plus PD-1 inhibitor or perioperative chemotherapy alone.
The primary endpoint is the complete response (CR) rate, defined as the composite of pathological complete response (pCR) and clinical complete response (cCR). The study aims to evaluate the efficacy and safety of adding PD-1 inhibitor to perioperative chemotherapy in LARC, and to validate post-radiotherapy β-HB elevation as a predictive biomarker for immunotherapy benefit.
- Conditions
- Rectal Cancer, Radiotherapy, Immunotherapy, Chemotherapy
- Being tested
- Short-course radiotherapy, Capecitabine, Oxaliplatin, TME surgery, PD -1/PD-L1 monoclonal antibody
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short-course radiotherapyRadiation
Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.
CapecitabineDrug
1000mg/m2, bid, po, d1-14,q3w
OxaliplatinDrug
130mg/m2, ivgtt, d1,q3w
TME surgeryProcedure or surgery
The surgery was performed 1 week after the end of neoadjuvant therapy.
PD -1/PD-L1 monoclonal antibodyDrug
200 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion.
Watch & Wait strategyOther
The Watch \& Wait (W\&W) strategy is an organ-preserving clinical management approach for patients with locally advanced rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy. In this strategy, definitive surgical resection (total mesorectal excision, TME) is withheld, and patients are instead managed with a standardized, intensive surveillance regimen to monitor for disease regrowth.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | β-HB-Positive (β-HB Elevation significantly)
* Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
* Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
* PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
* Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. Receives: Radiation: Short-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery; Drug: PD -1/PD-L1 monoclonal antibody; Other: Watch & Wait strategy |
| Arm B | Experimental | β-HB-Positive (β-HB Elevation significantly)
* Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
* Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
* Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. Receives: Radiation: Short-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery; Other: Watch & Wait strategy |
| Arm C | Experimental | β-HB-Negative (β-HB no Elevation)
* Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
* Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
* PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
* Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. Receives: Radiation: Short-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery; Drug: PD -1/PD-L1 monoclonal antibody; Other: Watch & Wait strategy |
| Arm D | Experimental | β-HB-Negative (β-HB no Elevation)
* Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
* Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
* Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. Receives: Radiation: Short-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery; Other: Watch & Wait strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete response (CR) rate
Defined as pathological complete response (pCR) + Clinical complete response (cCR)
Measured: an expected average of 12 months
Secondary outcomes (3)
3-year disease-Free Survival
The time from the first day of disease free (operation date) to local or distant recurrence, or the death event caused by any reason, whichever occurs first
Measured: an expected average of 3 years
Overall Survival
The time from the date of randomization to the death caused by any cause
Measured: an expected average of 5 years
Adverse events (AEs) were graded according to the NCI CTCAE version 5·0
Adverse events and surgical safety
Measured: an expected average of 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Oct 2027 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tao Zhang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tao Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Investigators
- Zhenyu Lin, Principal investigator, Huazhong University of Science and Technology Tongji Medical College Union Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07847229
- Sponsor's protocol ID
- Union-BHB-2
- Status last verified
- Oct 2026
- First submitted
- 23 Sep 2026
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Biomarker-Stratified Phase 2 Study: β-Hydroxybutyrate as a Predictive Biomarker for Short-Course Radiotherapy Followed by Chemotherapy Plus PD-1 Inhibitor Versus Chemotherapy Alone in Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT07847229
- Acronym / sponsor ID
- Union-BHB-2
- Conditions
- Rectal Cancer, Radiotherapy, Immunotherapy, Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- Tao ZhangUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 29 Sep 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, single-arm, biomarker-stratified, multicenter phase 2 clinical trial. All enrolled patients first receive short-course radiotherapy (SCRT), followed by measurement of serum β-hydroxybutyrate (β-HB) levels to calculate the post-radiotherapy elevation rate. Patients are stratified into an β-HB-positive stratum (elevation significantly) and an β-HB-negative stratum (no elevation), then randomized 1:1 within each stratum to receive either perioperative chemotherapy plus PD-1 inhibitor or perioperative chemotherapy alone.
The primary endpoint is the complete response (CR) rate, defined as the composite of pathological complete response (pCR) and clinical complete response (cCR). The study aims to evaluate the efficacy and safety of adding PD-1 inhibitor to perioperative chemotherapy in LARC, and to validate post-radiotherapy β-HB elevation as a predictive biomarker for immunotherapy benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Radiation: Short-course radiotherapy, Drug: Capecitabine, Drug: Oxaliplatin, Procedure: TME surgery, Drug: PD -1/PD-L1 monoclonal antibody, Other: Watch & Wait strategyβ-HB-Positive (β-HB Elevation significantly) * Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week. * Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion. * PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks). * Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. |
| Arm B | Experimental | Radiation: Short-course radiotherapy, Drug: Capecitabine, Drug: Oxaliplatin, Procedure: TME surgery, Other: Watch & Wait strategyβ-HB-Positive (β-HB Elevation significantly) * Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week. * Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion. * Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. |
| Arm C | Experimental | Radiation: Short-course radiotherapy, Drug: Capecitabine, Drug: Oxaliplatin, Procedure: TME surgery, Drug: PD -1/PD-L1 monoclonal antibody, Other: Watch & Wait strategyβ-HB-Negative (β-HB no Elevation) * Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week. * Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion. * PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks). * Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. |
| Arm D | Experimental | Radiation: Short-course radiotherapy, Drug: Capecitabine, Drug: Oxaliplatin, Procedure: TME surgery, Other: Watch & Wait strategyβ-HB-Negative (β-HB no Elevation) * Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week. * Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion. * Procedure: Restaging after 6 cycles; TME surgery or Watch \& Wait strategy per multidisciplinary evaluation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients or their family members agree to participate in the study and sign the informed consent form;
- Age 18-75 years, male or female;
- Histologically confirmed Locally Advanced rectal adenocarcinoma;
- inferior margin ≤ 10 cm from the anal verge;
- ECOG performance status score is 0-1;
Key exclusion criteria (3 listed)
- Patients with non-pMMR LARC；
- Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms;
- Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).
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 radiotherapyEligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy. | Radiation | Arm A, Arm B, Arm C, Arm D |
| Capecitabine1000mg/m2, bid, po, d1-14,q3w | Drug | Arm A, Arm B, Arm C, Arm D |
| Oxaliplatin130mg/m2, ivgtt, d1,q3w | Drug | Arm A, Arm B, Arm C, Arm D |
| TME surgeryThe surgery was performed 1 week after the end of neoadjuvant therapy. | Procedure or surgery | Arm A, Arm B, Arm C, Arm D |
| PD -1/PD-L1 monoclonal antibody200 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion. | Drug | Arm A, Arm C |
| Watch & Wait strategyThe Watch \& Wait (W\&W) strategy is an organ-preserving clinical management approach for patients with locally advanced rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy. In this strategy, definitive surgical resection (total mesorectal excision, TME) is withheld, and patients are instead managed with a standardized, intensive surveillance regimen to monitor for disease regrowth. | Other | Arm A, Arm B, Arm C, Arm D |
Primary outcome
complete response (CR) rate
Time frame: an expected average of 12 months
Defined as pathological complete response (pCR) + Clinical complete response (cCR)
3 secondary outcomes
3-year disease-Free Survival
Time frame: an expected average of 3 years
Overall Survival
Time frame: an expected average of 5 years
Adverse events (AEs) were graded according to the NCI CTCAE version 5·0
Time frame: an expected average of 1.5 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 6 Oct 2026.
- Individual participant dataSharing planned: Undecided
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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.
Tao Zhang contact
Zhenyu Lin principal investigator
Huazhong University of Science and Technology Tongji Medical College Union Hospital
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, Capecitabine and Oxaliplatin in people with Rectal Cancer and Radiotherapy, run by Tao Zhang 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 9 inclusion and 3 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: opening soon, as of the sponsor's last update on 6 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 Zhenyu Lin (15827130393, whxhlzy@hust.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: an expected average of 12 months). 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 6 Oct 2026; AzTrials last refreshed its copy on 31 Oct 2026.