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Clinical Trials in China / NCT07765667
Starting soon Phase 2

NCT + PD1 + Ketogenic Diet and/or Vitamin C for LARC

NCT07765667 · tracked via the Priya Life Science China tracker
Sponsor
Sixth Affiliated Hospital, Sun Yat-sen University
Phase
Phase 2
Started
2026-09-01
Last updated
2026-08-14

Condition(s) studied

Rectal AdenocarcinomaHigh-Risk CancerMSS

Investigational drug(s) / intervention(s)

Short-Course RadiotherapyPD-1 monoclonal antibodymFOLFOX6 regimenKetogenic DietSurgical resectionVitamin C

Short-Course Radiotherapy: Patients undergo SCRT at a dose of 5Gy × 5 fractions

PD-1 monoclonal antibody: Patients receive six cycles of immunotherapy with serplulimab injection, a PD-1 monoclonal antibody, at a fixed dose of 200 mg per cycle.

mFOLFOX6 regimen: 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 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 resection: Surgery either local excition or total mesorectal excision is performed 2 weeks after the completion of neoadjuvant therapy.

Vitamin C: 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 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 II clinical study, providing preliminary evidence for optimizing neoadjuvant treatment strategies for this population.

Eligibility

Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria: 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; * 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 1. 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. 2. Severe hypertension that is inadequately controlled with medication. 3. A history of human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C infection with a high viral DNA copy number. 4. Active tuberculosis (TB), current anti-tuberculosis treatment, or receipt of anti-tuberculosis treatment within 1 year before screening. 5. Other active, clinically serious infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. 6. Preoperative evidence of distant metastases outside the pelvis. 7. Cachexia or decompensated organ function. 8. Prior pelvic or abdominal radiotherapy. 9. Multiple primary colorectal cancers. 10. Confirmed glucose-6-phosphate dehydrogenase (G6PD) deficiency. 11. Seizures requiring treatment, such as corticosteroid or antiepileptic therapy. 12. A history of another malignancy within the previous 5 years, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin. 13. Substance abuse or any medical, psychological, or social condition that may interfere with participation in the study or the evaluation of study results. 14. 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. 15. Receipt of any vaccine against an infectious disease, such as an influenza or varicella vaccine, within 4 weeks before enrollment. 16. 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. 17. 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. 18. Known or suspected hypersensitivity to any study drug or to any medication administered in connection with this study. 19. Any unstable condition or other circumstance that may compromise participant safety or treatment compliance. 20. Pregnant or breastfeeding women, or women of childbearing potential who are not using adequate contraception. 21. Refusal to provide written informed consent.

Primary outcome measure(s)

Trial sites (1)

FacilityCityRegionStatus
Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou Guangdong

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07765667 on ClinicalTrials.gov ↗ ← All trials in China