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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Xuelei Ma, MD
- Telefonnummer: 13408410416
- E-mail: drmaxuelei@gmail.com
Studiesteder
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Sichuan
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Chengdu, Sichuan, Kina, 610041
- West China Hospital, Sichuan University
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Kontakt:
- Xuelei Ma, MD
- Telefonnummer: 13408410416
- E-mail: drmaxuelei@gmail.com
-
Ledende efterforsker:
- Xuelei Ma, MD
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
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Eksperimentel: 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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Aktiv komparator: 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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Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Complete Response Rate (pCR + cCR)
Tidsramme: 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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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Major Pathological Response (MPR) Rate
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: Up to 5 years after randomization.
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Up to 5 years after randomization.
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Progression-Free Survival (PFS)
Tidsramme: Up to 5 years after randomization.
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Up to 5 years after randomization.
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Overall Survival (OS)
Tidsramme: Up to 5 years after randomization.
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Up to 5 years after randomization.
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Incidence of Adverse Events
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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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Andre resultatmål
Andre resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Change in Gut Microbiome Diversity as Assessed by Metagenomic Sequencing
Tidsramme: 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
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- Approval No. 1280 (2026)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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