Advanced Gastric Cancer
Conditions
Keywords
Advanced Gastric Cancer, Leucine-Restricted Diet, Chemotherapy, Immunotherapy
Brief summary
Based on existing literature, we posit that a leucine-restricted diet is safe and well-tolerated in patients with advanced gastric cancer receiving combined chemotherapy and immunotherapy. Patients adhering to this dietary regimen exhibit a significant reduction in serum leucine concentrations, with no notable impact on the serum levels of other amino acids. Furthermore, leucine restriction promotes the activation of immune cells within the tumor microenvironment. When applied in conjunction with chemotherapy and immunotherapy for advanced gastric cancer, this approach demonstrates synergistic anti-tumor efficacy. It is expected to enhance tumor response rates , improve the 1-year survival rate, prolong overall survival (OS), and ultimately optimize patient prognosis.
Detailed description
This study employs a self-controlled design to comprehensively evaluate the safety and efficacy of a leucine-restricted diet combined with chemotherapy and immunotherapy in patients with advanced gastric cancer, with follow-up assessments of survival status to determine the 1-year survival rate and Overall Survival (OS). For patients eligible for R0 resection, anti-tumor efficacy will be pathologically assessed using the Tumor Regression Grade system, alongside statistical analysis of tumor response rates following combined therapy. Furthermore, the study will investigate mechanistic changes by comparing the tumor immune microenvironment and serum amino acid profiles (including leucine) before and after dietary intervention, while monitoring alterations in patient body composition, ultimately aiming to validate the hypothesis that leucine restriction enhances therapeutic outcomes in this setting.
Interventions
DIETARY_SUPPLEMENTLucine-restricted diet
During each hospitalization cycle for combined chemotherapy and immunotherapy, study participants will undergo a 3-day leucine-restricted diet concurrently with PD-1 inhibitor and chemotherapy administration; following this 3-day intervention period, the dietary restriction will be discontinued, and patients will gradually resume a normal diet.
Sponsors
Qilu Hospital of Shandong University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis and Treatment Plan: Patients with advanced gastric cancer with distant metastasis, confirmed by imaging modalities (such as CT or PET-CT) and clinical pathological data, who are indicated for combined chemotherapy and immunotherapy. * Demographics: Aged 18 to 70 years, regardless of gender. * Dietary Capability: Capable of oral intake or receiving liquid diet via nasogastric tube. * Consent: Willing to participate in this study and have signed the Informed Consent Form (ICF). * Exclusion of Other Malignancies: No concurrent primary malignant tumors other than gastric cancer.
Exclusion criteria
* Cognitive or Psychiatric Impairment: Cognitive dysfunction or psychiatric disorders that prevent the patient from understanding the study content or providing informed consent. * Diabetes Mellitus: Diagnosis of Type 1 or Type 2 diabetes mellitus. * Gastrointestinal Conditions: Presence of severe diarrhea, intractable vomiting, severe malabsorption syndrome, paralytic or mechanical intestinal obstruction, or active gastrointestinal bleeding. * Allergy：Known hypersensitivity or allergy to any of the main components of the leucine-deficient nutritional powder. * Concomitant Supplements: Current use of other nutritional supplements that may potentially confound the study results or affect efficacy evaluation. * Treatment Tolerance: Inability to tolerate combined chemotherapy and immunotherapy, or occurrence of severe gastrointestinal adverse events following such treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Evaluation Criteria in Solid Tumors (RECIST) Grade | 1 year after therapy | This scoring system includes four grades: CR, PR, PD, and SD, where CR stands for complete response, PR for partial response, PD for progressive disease, and SD for stable disease. |
| 1-year survival rate and overall survival (OS) | 1 year after surgery | This indicator is calculated by comprehensively summarizing the 1-year survival rate and overall survival. |
| The tumor regression grade (TRG) system | 1 month after surgery | TRG (Tumor Regression Grade) is used to assess pathological response after neoadjuvant therapy based on the 8th edition AJCC/CAP criteria. Different grades represent varying degrees of regression: TRG 0 indicates complete response (no residual tumor cells); TRG 1 indicates near-complete response (scattered residual tumor cells, \<10%); TRG 2 indicates partial response (residual tumor cells accounting for 10%-50%); TRG 3 indicates no or minimal response (residual tumor cells \>50%). Higher grades suggest poorer treatment efficacy. |
| Grade of CTCAE grading system | 6 months after therapy | This indicator was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) grading system, which comprises five grades (1-5). Grade 1 represents no or mild symptoms, while Grade 5 indicates death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Immune Microenvironment of Gastric Cancer Patients Following a Leucine-Restricted Diet | Measurements were performed prior to the initiation of the amino acid-restricted diet and on the day of surgery before the operation. | Comparative analysis of tumor scRNA-seq and ctDNA profiles pre- and post-diet, alongside flow cytometry-based assessment of circulating CD8+ T cells and ctDNA levels in blood samples. |
| Serum concentrations of various amino acids, including leucine, in patients with gastric cancer | Measurements were performed prior to the initiation of the amino acid-restricted diet and on the day of surgery before the operation. | Peripheral blood was collected for the determination of amino acid concentrations. |
Countries
China
Contacts
CONTACTHui Qu, Doctor of Medicine
Outcome results
None listed