Rectal AdenocarcinomaPhase 2CRI-KEVNCT07765667
NCT + PD1 + Ketogenic Diet and/or Vitamin C for LARC
A Phase 2 study testing Short-Course Radiotherapy, PD-1 monoclonal antibody and mFOLFOX6 regimen in people with Rectal Adenocarcinoma and High-Risk Cancer, run by Sixth Affiliated Hospital, Sun Yat-sen University at 1 site in China.
Trial summary
To explore the efficacy and safety of adding a ketogenic diet and/or high-dose intravenous vitamin C to neoadjuvant short-course radiotherapy followed by mFOLFOX6 chemotherapy combined with serplulimab in patients with locally advanced pMMR/MSS rectal adenocarcinoma through a prospective, randomized, controlled phase… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rectal Adenocarcinoma, High-Risk Cancer, MSS
- What is being tested?
- Short-Course Radiotherapy, PD-1 monoclonal antibody and mFOLFOX6 regimen
- Type of treatment
- Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2026to 1 Sep 2029
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Histologically confirmed rectal adenocarcinoma. 2. Age 18-80 years. 3. Immunohistochemical examination of biopsy specimens indicating proficient mismatch repair (pMMR), or microsatellite-stable (MSS) status.
- 4. Clinical stage cT3-T4N0 or cTxN+. 5. The lower margin of the rectal tumor is ≤10 cm from the anal verge. 6. No distant metastases, as confirmed by contrast-enhanced CT of the chest, abdomen, and pelvis and pelvic MRI before treatment.
- 7. No evidence of intestinal obstruction, or resolution of obstruction following diverting stoma surgery.
- 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 9. Adequate peripheral blood counts and hepatic and renal function, as defined by the following laboratory values measured within 15 days before treatment initiation:
- White blood cell count (WBC) ≥3.0 × 10⁹/L or absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;
- Hemoglobin (HGB) ≥80 g/L;
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- Platelet count (PLT) ≥100 × 10⁹/L;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3.0 × the upper limit of normal (ULN);
- Total bilirubin (TBIL) <1.5 × ULN;
- Serum creatinine (CREAT) <1.5 × ULN. 10. No prior chemotherapy or radiotherapy. 11. No prior treatment with biological agents (e.g., monoclonal antibodies), immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies), or other investigational agents.
- 12. Not pregnant or breastfeeding. Participants must use effective contraception during the study and for 6 months after the final dose of study treatment.
- 13. Written informed consent has been provided. Exclusion Criteria
- Arrhythmia requiring antiarrhythmic therapy, except for beta-blockers or digoxin; symptomatic coronary artery disease; myocardial ischemia, including myocardial infarction within the previous 6 months; or congestive heart failure greater than New York Heart Association (NYHA) class II.
- Severe hypertension that is inadequately controlled with medication.
- A history of human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C infection with a high viral DNA copy number.
- Active tuberculosis (TB), current anti-tuberculosis treatment, or receipt of anti-tuberculosis treatment within 1 year before screening.
- Other active, clinically serious infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
- Preoperative evidence of distant metastases outside the pelvis.
- Cachexia or decompensated organ function.
- Prior pelvic or abdominal radiotherapy.
- Multiple primary colorectal cancers.
- Confirmed glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Seizures requiring treatment, such as corticosteroid or antiepileptic therapy.
- A history of another malignancy within the previous 5 years, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin.
- Substance abuse or any medical, psychological, or social condition that may interfere with participation in the study or the evaluation of study results.
- Any active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, or hypothyroidism. Participants with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be enrolled; participants with asthma requiring medical intervention with bronchodilators are excluded.
- Receipt of any vaccine against an infectious disease, such as an influenza or varicella vaccine, within 4 weeks before enrollment.
- A concomitant condition requiring long-term immunosuppressive therapy or systemic or topical corticosteroids at immunosuppressive doses, defined as >10 mg/day of prednisone or an equivalent corticosteroid.
- Gastrointestinal disorders, such as an active gastric or duodenal ulcer, ulcerative colitis, or an unresected tumor with active bleeding; any other condition that may cause gastrointestinal bleeding or perforation; or an unhealed gastrointestinal perforation following surgery.
- Known or suspected hypersensitivity to any study drug or to any medication administered in connection with this study.
- Any unstable condition or other circumstance that may compromise participant safety or treatment compliance.
- Pregnant or breastfeeding women, or women of childbearing potential who are not using adequate contraception.
- Refusal to provide written informed consent.
Who cannot join
None listed.
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
Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong
Jun Huang, MD, +86-13926451242, huangj97@mail.sysu.edu.cn
Guohui Wan, PhD.
About this study
Official title: Neoadjuvant Chemoradiotherapy and Immunotherapy Combined With Ketogenic Diet and/or High-Dose Intravenous Vitamin C in pMMR/MSS Locally Advanced Rectal Adenocarcinoma: A Prospective, Multicenter, Phase Ⅱ Clinical Study (CRI-KEV Trial)
To explore the efficacy and safety of adding a ketogenic diet and/or high-dose intravenous vitamin C to neoadjuvant short-course radiotherapy followed by mFOLFOX6 chemotherapy combined with serplulimab in patients with locally advanced pMMR/MSS rectal adenocarcinoma through a prospective, randomized, controlled phase II clinical study, providing preliminary evidence for optimizing neoadjuvant treatment strategies for this population.
Read the detailed description
Patients with locally advanced rectal adenocarcinoma characterized by proficient mismatch repair or microsatellite stability (pMMR/MSS) generally derive limited benefit from immune checkpoint inhibitor monotherapy. Metabolic interventions may enhance the efficacy of chemotherapy and immunotherapy by modulating tumor metabolism and the tumor immune microenvironment. High-dose vitamin C has multitarget antitumor effects. Preclinical evidence suggests that it may activate the AMPK pathway, downregulate PD-L1 expression in colorectal cancer cells, and promote T-cell infiltration into the tumor microenvironment, thereby providing a mechanistic rationale for its combination with PD-1 blockade. In the phase III VITALITY trial, high-dose intravenous vitamin C combined with chemotherapy did not significantly improve progression-free survival in the overall population with metastatic colorectal cancer; however, a prespecified subgroup analysis demonstrated prolonged progression-free survival among patients with RAS-mutant tumors. A ketogenic diet may also exert antitumor effects by altering glucose availability, cellular energy metabolism, and the immune microenvironment. Emerging evidence suggests that dietary patterns, including high-fiber diets in patients receiving immunotherapy and ketogenic diets in those receiving chemotherapy, may be associated with improved treatment responses, although these findings require prospective validation. Therefore, this study aims to investigate whether adding a ketogenic diet and/or high-dose intravenous vitamin C to short-course radiotherapy followed by mFOLFOX6 chemotherapy combined with the PD-1 monoclonal antibody serplulimab can improve the pathological complete response and organ preservation rates in patients with locally advanced pMMR/MSS rectal adenocarcinoma. The efficacy and safety of four treatment strategies-no metabolic intervention, a ketogenic diet alone, high-dose intravenous vitamin C alone, and their combination-will be evaluated.
- Conditions
- Rectal Adenocarcinoma, High-Risk Cancer, MSS
- Being tested
- Short-Course Radiotherapy, PD-1 monoclonal antibody, mFOLFOX6 regimen, Ketogenic Diet, Surgical resection
- Keywords
- Targeting Therapy, Immunotherapy, Short-Course Radiotherapy, Ketogenic Diet, High-dose Intravenous Vitamin C
- 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
Also called SCRT
Patients undergo SCRT at a dose of 5Gy × 5 fractions
PD-1 monoclonal antibodyDrug
Also called PD-1
Patients receive six cycles of immunotherapy with serplulimab injection, a PD-1 monoclonal antibody, at a fixed dose of 200 mg per cycle.
mFOLFOX6 regimenCombination product
Also called mFOLFOX6
Patients receive six cycles of the mFOLFOX6 regimen, consisting of oxaliplatin (85 mg/m²) and leucovorin (200 mg/m²) administered intravenously over 2 hours, followed by a bolus of fluorouracil (400 mg/m²) and a continuous infusion of fluorouracil (2,400 mg/m²) over 46 hours.
Ketogenic DietBehavioural
Also called Modified Atkins Diet
A modified Atkins diet (MAD) is used, with the goal of maintaining nutritional ketosis, defined as a blood β-hydroxybutyrate (BHB) level of 1.5-3.0 mmol/L. The ketogenic dietary intervention begins after completion of SCRT and continues throughout six cycles of mFOLFOX6 chemotherapy and immunotherapy until the completion of neoadjuvant treatment.
Surgical resectionProcedure or surgery
Also called Surgery
Surgery either local excition or total mesorectal excision is performed 2 weeks after the completion of neoadjuvant therapy.
Vitamin CDrug
Also called VitC
Vitamin C is administered intravenously at a dose of 1.5 g/kg/day, diluted in 250-500 mL of normal saline, over 2 hours for 3 consecutive days (Days 1-3). Each treatment cycle is repeated every 2 weeks and synchronized with the neoadjuvant treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 | Sham comparator | The neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen and PD-1 monoclonal antibody. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. At least 7 days after the completion of radiotherapy, patients complete 6 cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody at two-week intervals. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. Receives: Radiation: Short-Course Radiotherapy; Drug: PD-1 monoclonal antibody; Combination Product: mFOLFOX6 regimen; Procedure: Surgical resection |
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet | Experimental | The neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody and daily ketogenic diet. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. After completing radiotherapy, patients initiate a ketogenic dietary intervention and, at least 7 days later, receive six cycles of mFOLFOX6 chemotherapy combined with a PD-1 monoclonal antibody at two-week intervals. The ketogenic dietary intervention continues until the completion of neoadjuvant treatment. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. Receives: Radiation: Short-Course Radiotherapy; Drug: PD-1 monoclonal antibody; Combination Product: mFOLFOX6 regimen; Behavioral: Ketogenic Diet; Procedure: Surgical resection |
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C | Experimental | The neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody and Vitamin C. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. At least 7 days after the completion of radiotherapy, patients complete 6 cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody and at two-week intervals, together with intravenous vitamin C at 1.5 g/kg/day on three consecutive days (Days 1-3) of each cycle. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. Receives: Radiation: Short-Course Radiotherapy; Drug: PD-1 monoclonal antibody; Combination Product: mFOLFOX6 regimen; Procedure: Surgical resection; Drug: Vitamin C |
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C | Experimental | The neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody, Vitamin C and daily ketogenic diet. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. After completing radiotherapy, patients initiate a ketogenic dietary intervention and, at least 7 days later, receive six cycles of mFOLFOX6 chemotherapy combined with a PD-1 monoclonal antibody at two-week intervals, together with intravenous vitamin C at 1.5 g/kg/day on three consecutive days (Days 1-3) of each cycle. The ketogenic dietary intervention continues until the completion of neoadjuvant treatment. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. Receives: Radiation: Short-Course Radiotherapy; Drug: PD-1 monoclonal antibody; Combination Product: mFOLFOX6 regimen; Behavioral: Ketogenic Diet; Procedure: Surgical resection; Drug: Vitamin C |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR rate
Pathological complete response rate, ypT0N0 for TME surgery and ypT0rN0 for local excision
Measured: 1 year
Secondary outcomes (7)
Adverse Events Associated with Neoadjuvant Therapy
Incidence of adverse events related to neoadjuvant therapy as assessed by CTCAE v5.0
Measured: 1 year
MPR
Major pathological response rate
Measured: 1 year
Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate
Completion rate of neoadjuvant therapy
Measured: 1 year
R0 resection rate
R0 resection rate in participants
Measured: 1 year
TRG
Tumor regression grade
Measured: 1 year
3 years DFS Rate
3 years Disease Free Survival Rate
Measured: 3 years
3 years OS rate
3 years Overall Survival Rate
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Sixth Affiliated Hospital, 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
- Factorial
- Model description
- This is a prospective, open-label, phase II study with a 2 × 2 factorial design. All participants receive short-course radiotherapy followed by six cycles of mFOLFOX6 chemotherapy combined with a PD-1 monoclonal antibody. Participants are assigned to one of four groups: no metabolic intervention, a ketogenic diet alone, high-dose intravenous vitamin C alone, or the combination of a ketogenic diet and high-dose intravenous vitamin C. A Simon optimal two-stage design is applied separately to each of the three experimental groups.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jun Huang, Sixth Affiliated Hospital, Sun Yat-sen University
- Investigators
- Jun Huang, PhD., Study chair, 6th Affliated Hospital of Sun Yat-sen UniversityGuohui Wan, PhD., Principal investigator, School of Pharmaceutical Sciences, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07765667
- Sponsor's protocol ID
- E2026243
- Acronym
- CRI-KEV
- Status last verified
- Aug 2026
- First submitted
- 11 Aug 2026
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Chemoradiotherapy and Immunotherapy Combined With Ketogenic Diet and/or High-Dose Intravenous Vitamin C in pMMR/MSS Locally Advanced Rectal Adenocarcinoma: A Prospective, Multicenter, Phase Ⅱ Clinical Study (CRI-KEV Trial)
- ClinicalTrials.gov ID
- NCT07765667
- Acronym / sponsor ID
- CRI-KEV / E2026243
- Conditions
- Rectal Adenocarcinoma, High-Risk Cancer, MSS
- Keywords
- Targeting Therapy, Immunotherapy, Short-Course Radiotherapy, Ketogenic Diet, High-dose Intravenous Vitamin C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sixth Affiliated Hospital, Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2029 (estimated)
- Study completion
- 1 Sep 2029 (estimated)
- First posted
- 14 Aug 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.
To explore the efficacy and safety of adding a ketogenic diet and/or high-dose intravenous vitamin C to neoadjuvant short-course radiotherapy followed by mFOLFOX6 chemotherapy combined with serplulimab in patients with locally advanced pMMR/MSS rectal adenocarcinoma through a prospective, randomized, controlled phase II clinical study, providing preliminary evidence for optimizing neoadjuvant treatment strategies for this population.
Detailed description
Patients with locally advanced rectal adenocarcinoma characterized by proficient mismatch repair or microsatellite stability (pMMR/MSS) generally derive limited benefit from immune checkpoint inhibitor monotherapy. Metabolic interventions may enhance the efficacy of chemotherapy and immunotherapy by modulating tumor metabolism and the tumor immune microenvironment. High-dose vitamin C has multitarget antitumor effects. Preclinical evidence suggests that it may activate the AMPK pathway, downregulate PD-L1 expression in colorectal cancer cells, and promote T-cell infiltration into the tumor microenvironment, thereby providing a mechanistic rationale for its combination with PD-1 blockade. In the phase III VITALITY trial, high-dose intravenous vitamin C combined with chemotherapy did not significantly improve progression-free survival in the overall population with metastatic colorectal cancer; however, a prespecified subgroup analysis demonstrated prolonged progression-free survival among patients with RAS-mutant tumors. A ketogenic diet may also exert antitumor effects by altering glucose availability, cellular energy metabolism, and the immune microenvironment. Emerging evidence suggests that dietary patterns, including high-fiber diets in patients receiving immunotherapy and ketogenic diets in those receiving chemotherapy, may be associated with improved treatment responses, although these findings require prospective validation. Therefore, this study aims to investigate whether adding a ketogenic diet and/or high-dose intravenous vitamin C to short-course radiotherapy followed by mFOLFOX6 chemotherapy combined with the PD-1 monoclonal antibody serplulimab can improve the pathological complete response and organ preservation rates in patients with locally advanced pMMR/MSS rectal adenocarcinoma. The efficacy and safety of four treatment strategies-no metabolic intervention, a ketogenic diet alone, high-dose intravenous vitamin C alone, and their combination-will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This is a prospective, open-label, phase II study with a 2 × 2 factorial design. All participants receive short-course radiotherapy followed by six cycles of mFOLFOX6 chemotherapy combined with a PD-1 monoclonal antibody. Participants are assigned to one of four groups: no metabolic intervention, a ketogenic diet alone, high-dose intravenous vitamin C alone, or the combination of a ketogenic diet and high-dose intravenous vitamin C. A Simon optimal two-stage design is applied separately to each of the three experimental groups.
| Arm | Type | Receives |
|---|---|---|
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 | Sham comparator | Radiation: Short-Course Radiotherapy, Drug: PD-1 monoclonal antibody, Combination Product: mFOLFOX6 regimen, Procedure: Surgical resectionThe neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen and PD-1 monoclonal antibody. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. At least 7 days after the completion of radiotherapy, patients complete 6 cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody at two-week intervals. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. |
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet | Experimental | Radiation: Short-Course Radiotherapy, Drug: PD-1 monoclonal antibody, Combination Product: mFOLFOX6 regimen, Behavioral: Ketogenic Diet, Procedure: Surgical resectionThe neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody and daily ketogenic diet. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. After completing radiotherapy, patients initiate a ketogenic dietary intervention and, at least 7 days later, receive six cycles of mFOLFOX6 chemotherapy combined with a PD-1 monoclonal antibody at two-week intervals. The ketogenic dietary intervention continues until the completion of neoadjuvant treatment. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. |
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C | Experimental | Radiation: Short-Course Radiotherapy, Drug: PD-1 monoclonal antibody, Combination Product: mFOLFOX6 regimen, Procedure: Surgical resection, Drug: Vitamin CThe neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody and Vitamin C. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. At least 7 days after the completion of radiotherapy, patients complete 6 cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody and at two-week intervals, together with intravenous vitamin C at 1.5 g/kg/day on three consecutive days (Days 1-3) of each cycle. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. |
| Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C | Experimental | Radiation: Short-Course Radiotherapy, Drug: PD-1 monoclonal antibody, Combination Product: mFOLFOX6 regimen, Behavioral: Ketogenic Diet, Procedure: Surgical resection, Drug: Vitamin CThe neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with 6 cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody, Vitamin C and daily ketogenic diet. Initially, patients undergo SCRT at a dose of 5Gy × 5 fractions. After completing radiotherapy, patients initiate a ketogenic dietary intervention and, at least 7 days later, receive six cycles of mFOLFOX6 chemotherapy combined with a PD-1 monoclonal antibody at two-week intervals, together with intravenous vitamin C at 1.5 g/kg/day on three consecutive days (Days 1-3) of each cycle. The ketogenic dietary intervention continues until the completion of neoadjuvant treatment. Surgery is performed 2 weeks after the completion of the last cycle of chemotherapy. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- 1. Histologically confirmed rectal adenocarcinoma. 2. Age 18-80 years. 3. Immunohistochemical examination of biopsy specimens indicating proficient mismatch repair (pMMR), or microsatellite-stable (MSS) status.
- 4. Clinical stage cT3-T4N0 or cTxN+. 5. The lower margin of the rectal tumor is ≤10 cm from the anal verge. 6. No distant metastases, as confirmed by contrast-enhanced CT of the chest, abdomen, and pelvis and pelvic MRI before treatment.
- 7. No evidence of intestinal obstruction, or resolution of obstruction following diverting stoma surgery.
- 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 9. Adequate peripheral blood counts and hepatic and renal function, as defined by the following laboratory values measured within 15 days before treatment initiation:
- White blood cell count (WBC) ≥3.0 × 10⁹/L or absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;
Key exclusion criteria (0 listed)
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 RadiotherapyAlso: SCRTPatients undergo SCRT at a dose of 5Gy × 5 fractions | Radiation | Short-Course Radiotherapy + mFOLFOX6 + PD-1, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C |
| PD-1 monoclonal antibodyAlso: PD-1Patients receive six cycles of immunotherapy with serplulimab injection, a PD-1 monoclonal antibody, at a fixed dose of 200 mg per cycle. | Drug | Short-Course Radiotherapy + mFOLFOX6 + PD-1, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C |
| mFOLFOX6 regimenAlso: mFOLFOX6Patients receive six cycles of the mFOLFOX6 regimen, consisting of oxaliplatin (85 mg/m²) and leucovorin (200 mg/m²) administered intravenously over 2 hours, followed by a bolus of fluorouracil (400 mg/m²) and a continuous infusion of fluorouracil (2,400 mg/m²) over 46 hours. | Combination product | Short-Course Radiotherapy + mFOLFOX6 + PD-1, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C |
| Ketogenic DietAlso: Modified Atkins DietA modified Atkins diet (MAD) is used, with the goal of maintaining nutritional ketosis, defined as a blood β-hydroxybutyrate (BHB) level of 1.5-3.0 mmol/L. The ketogenic dietary intervention begins after completion of SCRT and continues throughout six cycles of mFOLFOX6 chemotherapy and immunotherapy until the completion of neoadjuvant treatment. | Behavioural | Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C |
| Surgical resectionAlso: SurgerySurgery either local excition or total mesorectal excision is performed 2 weeks after the completion of neoadjuvant therapy. | Procedure or surgery | Short-Course Radiotherapy + mFOLFOX6 + PD-1, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C |
| Vitamin CAlso: VitCVitamin C is administered intravenously at a dose of 1.5 g/kg/day, diluted in 250-500 mL of normal saline, over 2 hours for 3 consecutive days (Days 1-3). Each treatment cycle is repeated every 2 weeks and synchronized with the neoadjuvant treatment cycle. | Drug | Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C, Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C |
Primary outcome
pCR rate
Time frame: 1 year
Pathological complete response rate, ypT0N0 for TME surgery and ypT0rN0 for local excision
7 secondary outcomes
Adverse Events Associated with Neoadjuvant Therapy
Time frame: 1 year
MPR
Time frame: 1 year
Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate
Time frame: 1 year
R0 resection rate
Time frame: 1 year
TRG
Time frame: 1 year
3 years DFS Rate
Time frame: 3 years
3 years OS rate
Time frame: 3 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 14 Aug 2026.
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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.
Jun Huang, PhD. study chair
6th Affliated Hospital of Sun Yat-sen University
Guohui Wan, PhD. principal investigator
School of Pharmaceutical Sciences, 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, PD-1 monoclonal antibody and mFOLFOX6 regimen in people with Rectal Adenocarcinoma and High-Risk Cancer, run by Sixth Affiliated Hospital, 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 33 inclusion and 0 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 14 Aug 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. Some participants in this study may receive a placebo. 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 Jun Huang, PhD. (+8613926451242, huangj97@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pCR rate (time frame: 1 year). 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 14 Aug 2026.