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

NCT07765667 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: E2026243
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rectal Adenocarcinoma; High-Risk Cancer; MSS

Keywords

Targeting Therapy; Immunotherapy; Short-Course Radiotherapy; Ketogenic Diet; High-dose Intravenous Vitamin C

Outcome Measures

Primary Outcomes (1)

• pCR rate

  Pathological complete response rate, ypT0N0 for TME surgery and ypT0rN0 for local excision

  1 year

Secondary Outcomes (7)

• Adverse Events Associated with Neoadjuvant Therapy

  1 year

• MPR

  1 year

• Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate Neoadjuvant therapy completion rate

  1 year

• R0 resection rate

  1 year

• TRG

  1 year

Study Arms (4)

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.

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.

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.

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.

Radiation: Short-Course Radiotherapy; Drug: PD-1 monoclonal antibody; Combination Product: mFOLFOX6 regimen; Behavioral: Ketogenic Diet; Procedure: Surgical resection; Drug: Vitamin C

Interventions

Short-Course Radiotherapy RADIATION

Patients undergo SCRT at a dose of 5Gy × 5 fractions

Also known as: SCRT

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 antibody DRUG

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

Also known as: PD-1

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 regimen COMBINATION_PRODUCT

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.

Also known as: mFOLFOX6

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 Diet BEHAVIORAL

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.

Also known as: Modified Atkins Diet

Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet; Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C

Surgical resection PROCEDURE

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

Also known as: 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 C DRUG

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.

Also known as: VitC

Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Ketogenic Diet + Vitamin C; Short-Course Radiotherapy + mFOLFOX6 + PD-1 + Vitamin C

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. 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.
• \. No evidence of intestinal obstruction, or resolution of obstruction following diverting stoma surgery.
• \. 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.
• \. Not pregnant or breastfeeding. Participants must use effective contraception during the study and for 6 months after the final dose of study treatment.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

spartalizumab; Diet, Ketogenic; Surgical Procedures, Operative; Ascorbic Acid

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Jun Huang, PhD.

  6th Affliated Hospital of Sun Yat-sen University

  STUDY CHAIR

• Guohui Wan, PhD.

  School of Pharmaceutical Sciences, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Huang, PhD.

CONTACT

+8613926451242; huangj97@mail.sysu.edu.cn

Fang He, MD.

CONTACT

+8618826059789; hefang23@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: August 11, 2026
• First Posted: August 14, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 14, 2026

Record last verified: 2026-08

Locations

CN (1)