- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07811076
Serine/Glycine-Restricted Diet With Chemoradiotherapy for Rectal Cancer (SG-RCT)
A Randomized Controlled Trial of Serine/Glycine-Restricted Diet Combined With Chemoradiotherapy and Immunotherapy for Neoadjuvant Treatment of Rectal Cancer
This is a Phase Ib/II seamless, open-label, randomized controlled trial evaluating the safety and efficacy of a serine/glycine-restricted diet combined with neoadjuvant chemoradiotherapy and immunotherapy in patients with locally advanced rectal cancer (LARC).
The study consists of two phases. Phase Ib is a non-randomized, single-arm safety run-in phase enrolling 6 patients, all of whom will receive the experimental regimen (serine/glycine-restricted diet plus CAPOX chemotherapy, PD-1 inhibitor, and short-course radiotherapy). The primary objective of Phase Ib is to assess safety, tolerability, and dietary compliance. If the safety criteria are met (≥3 grade diet-related adverse event rate ≤20% and compliance rate ≥70%), the study will proceed to Phase II.
Phase II is a randomized, open-label, parallel-controlled phase in which 134 additional patients will be randomized in a 1:1 ratio to either the experimental group (serine/glycine-restricted diet plus standard neoadjuvant chemoradiotherapy and immunotherapy) or the control group (standard neoadjuvant chemoradiotherapy and immunotherapy alone). The total enrollment is 140 patients (6 in Phase Ib + 134 in Phase II).
The primary endpoint is the complete response rate (pCR + cCR). Secondary endpoints include major pathological response (MPR) rate, R0 resection rate, mrTRG regression grade, event-free survival (EFS), progression-free survival (PFS), overall survival (OS), adverse event profile, changes in serum amino acid levels, quality of life (EORTC QLQ-C30), and nutritional status. Exploratory endpoints include gut microbiome diversity and tumor immune microenvironment changes.
Descripción general del estudio
Estado
Condiciones
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Xuelei Ma, MD
- Número de teléfono: 13408410416
- Correo electrónico: drmaxuelei@gmail.com
Ubicaciones de estudio
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Sichuan
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Chengdu, Sichuan, Porcelana, 610041
- West China Hospital, Sichuan University
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Contacto:
- Xuelei Ma, MD
- Número de teléfono: 13408410416
- Correo electrónico: drmaxuelei@gmail.com
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Investigador principal:
- Xuelei Ma, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Written informed consent obtained prior to any study-related procedures.
- Male or female, aged 18-80 years.
- Histologically confirmed locally advanced rectal cancer staged as cT3, cT4, or node-positive by pelvic MRI.
- ECOG performance status score of 0 or 1.
- NRS-2002 score < 3 (no significant nutritional risk).
- BMI ≥ 18.5 kg/m² (may be adjusted per actual conditions).
- Capable of oral intake or via feeding tube and able to tolerate enteral nutrition.
- Adequate organ function as defined by the following laboratory criteria:
ANC ≥ 1.5×10⁹/L (without G-CSF support within 14 days); Platelet count ≥ 100×10⁹/L; Hemoglobin ≥ 9 g/dL (without transfusion or erythropoietin use within 7 days); Serum albumin ≥ 3.0 g/dL; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5× ULN; Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula) or serum creatinine ≤ 1.5× ULN; INR ≤ 1.5× ULN, PT and APTT ≤ 1.5× ULN; Urine protein < 2+ (if ≥2+, 24-hour urine protein < 2.0 g required for enrollment); Cardiac enzymes within normal range (isolated laboratory abnormalities without clinical significance permitted).
- Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to study treatment initiation and agree to use highly effective contraception from signing informed consent through at least 6 months after the last dose of study treatment.
- All patients (male or female) at risk of pregnancy must use contraceptive methods with a failure rate < 1% per year throughout the treatment period and up to 120 days after the last dose of study treatment (or 180 days after the last dose of chemotherapy).
Exclusion Criteria:
- Stage I or Stage IV rectal cancer.
- Cognitive impairment or psychiatric disorders that prevent comprehension of the study content.
- Central nervous system or meningeal metastases.
- Clinically symptomatic moderate to severe ascites (requiring therapeutic paracentesis within 2 weeks before study treatment start; patients with small asymptomatic ascites may be enrolled).
- Uncontrolled or moderate to severe pleural effusion and pericardial effusion.
- Severe diarrhea, intractable vomiting, severe malabsorption syndrome, paralytic or mechanical intestinal obstruction; tracheoesophageal fistula, gastrointestinal perforation or fistula, or intra-abdominal abscess; gastrointestinal bleeding (CTCAE grade ≥ 3 within 6 months or grade ≥ 2 within 3 months before study treatment start, e.g., abnormal vaginal bleeding, hematemesis).
- Any other condition that may affect the study results or lead to forced discontinuation (e.g., alcohol abuse, drug abuse, serious concurrent diseases, severe laboratory abnormalities, family or social factors) as judged by the investigator.
- Known allergy to any active ingredient or excipient of the study drugs or nutritional powder.
- Poorly controlled diabetes mellitus.
- Severe cardiovascular disease, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction, or major vascular disease within 6 months prior to enrollment; uncontrolled symptomatic cardiac disease such as unstable angina, NYHA class II or higher heart failure, LVEF < 50% on echocardiography, or severe arrhythmia not controlled by medication.
- Pregnancy or lactation.
- Any other condition that the investigator considers unsuitable for enrollment.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Serine/Glycine-Restricted Diet Plus Chemoradiotherapy and Immunotherapy
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A specialized liquid nutritional powder free of serine and glycine, supplemented with a list of permitted low-serine/glycine foods.
Patients receive 30 kcal/kg/day energy and 1.5 g/kg/day protein for 4 weeks during the neoadjuvant treatment period.
Oxaliplatin 130 mg/m² IV on day 1 of each 3-week cycle, plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each cycle, for a total of 6 cycles.
PD-1 inhibitor administered intravenously every 3 weeks in combination with CAPOX chemotherapy as part of the neoadjuvant regimen.
25 Gy delivered in 5 fractions (5 Gy/fraction) over 1 week, administered during the second week of Cycle 1 (C2, Week 1), concurrent with capecitabine.
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Comparador activo: Chemoradiotherapy and Immunotherapy Without Dietary Restriction
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Oxaliplatin 130 mg/m² IV on day 1 of each 3-week cycle, plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each cycle, for a total of 6 cycles.
PD-1 inhibitor administered intravenously every 3 weeks in combination with CAPOX chemotherapy as part of the neoadjuvant regimen.
25 Gy delivered in 5 fractions (5 Gy/fraction) over 1 week, administered during the second week of Cycle 1 (C2, Week 1), concurrent with capecitabine.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Complete Response Rate (pCR + cCR)
Periodo de tiempo: At the time of surgery, approximately 6-8 weeks after completion of all 6 cycles of neoadjuvant chemoradiotherapy and immunotherapy
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At the time of surgery, approximately 6-8 weeks after completion of all 6 cycles of neoadjuvant chemoradiotherapy and immunotherapy
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Major Pathological Response (MPR) Rate
Periodo de tiempo: At the time of radical surgery, approximately 24 weeks after initiation of neoadjuvant treatment.
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At the time of radical surgery, approximately 24 weeks after initiation of neoadjuvant treatment.
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R0 Resection Rate
Periodo de tiempo: At the time of radical surgery, approximately 24 weeks after initiation of neoadjuvant treatment.
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At the time of radical surgery, approximately 24 weeks after initiation of neoadjuvant treatment.
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mrTRG Regression Grade
Periodo de tiempo: Up to approximately 24 weeks after initiation of neoadjuvant treatment (at the time of pre-surgery imaging assessment).
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Up to approximately 24 weeks after initiation of neoadjuvant treatment (at the time of pre-surgery imaging assessment).
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Event-Free Survival (EFS)
Periodo de tiempo: Up to 5 years after randomization.
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Up to 5 years after randomization.
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Progression-Free Survival (PFS)
Periodo de tiempo: Up to 5 years after randomization.
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Up to 5 years after randomization.
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Overall Survival (OS)
Periodo de tiempo: Up to 5 years after randomization.
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Up to 5 years after randomization.
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Incidence of Adverse Events
Periodo de tiempo: From the start of study treatment through 30 days after the last dose of study treatment (approximately up to 22 weeks for the active treatment phase).
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From the start of study treatment through 30 days after the last dose of study treatment (approximately up to 22 weeks for the active treatment phase).
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Changes in Serum Amino Acid Levels
Periodo de tiempo: Baseline and at cycles 1, 2, and 3 (weeks 3, 6, and 9) during the intervention phase.
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Baseline and at cycles 1, 2, and 3 (weeks 3, 6, and 9) during the intervention phase.
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Quality of Life (EORTC QLQ-C30)
Periodo de tiempo: Baseline, at cycles 1, 2, 3, 4, 5, 6 (weeks 3, 6, 9, 12, 15, 18), and at 30-day safety follow-up.
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Baseline, at cycles 1, 2, 3, 4, 5, 6 (weeks 3, 6, 9, 12, 15, 18), and at 30-day safety follow-up.
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Nutritional Status
Periodo de tiempo: Baseline, at cycles 1, 2, and 3 (weeks 3, 6, and 9), and at surgery.
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Baseline, at cycles 1, 2, and 3 (weeks 3, 6, and 9), and at surgery.
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Otras medidas de resultado
Medida de resultado |
Periodo de tiempo |
|---|---|
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Change in Gut Microbiome Diversity as Assessed by Metagenomic Sequencing
Periodo de tiempo: Baseline and at the end of the dietary intervention period (week 4).
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Baseline and at the end of the dietary intervention period (week 4).
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Changes in Tumor-Infiltrating CD8⁺ T Cell Density and PD-L1 Expression as Assessed by Multiplex Immunohistochemistry
Periodo de tiempo: At the time of radical surgery, approximately 24 weeks after initiation of neoadjuvant treatment.
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At the time of radical surgery, approximately 24 weeks after initiation of neoadjuvant treatment.
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- Approval No. 1280 (2026)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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