Nutritional + Usual Corticosteroids Randomized Trial for Immune-Related pneumoniA - Therapeutic Utilization Evaluation

Официальное название

A Single-Center, Open-Label, Randomized Controlled Clinical Trial Comparing Nutritional Therapy (Spirulina-Bifidobacterium Capsules, Fish Oil-Grape Seed-Blueberry Soft Capsules, and Ganoderma Spore Oil) Combined With Standard Glucocorticoid Regimen Versus Standard Glucocorticoid Regimen Alone in the Treatment of Immune Checkpoint Inhibitor-Related Pneumonitis

Обзор

This is a prospective, single-center, open-label, randomized controlled clinical trial evaluating whether the addition of a nutritional therapy regimen (Spirulina-Bifidobacterium capsules, fish oil-grape seed-blueberry soft capsules, and Ganoderma spore oil) to standard glucocorticoid therapy improves outcomes in patients with Grade 3-4 immune checkpoint inhibitor-related pneumonitis (CIP), compared with standard glucocorticoid therapy alone. A total of 60 patients with malignancies who develop Grade 3-4 CIP (per CTCAE v5.0) after at least one cycle of immune checkpoint inhibitor therapy will be randomized 1:1 to the experimental or control arm. The primary endpoints are time to pneumonitis downgrading and the proportion of patients achieving downgrading at 3 months.

Подробное описание

BACKGROUND:

Immune checkpoint inhibitor-related pneumonitis (CIP) accounts for the largest proportion of fatal immune-related adverse events. Approximately 30% of patients respond poorly to corticosteroid therapy, and long-term high-dose steroids increase the risk of secondary infection. Oxidative stress plays a key role in pulmonary fibrosis. The investigational nutritional products have demonstrated antioxidant and immunomodulatory properties in preclinical and clinical studies.

OBJECTIVES:

Primary: To evaluate the efficacy of nutritional therapy combined with glucocorticoids versus glucocorticoids alone in treating CIP, as measured by time to pneumonitis downgrading and the 3-month downgrading rate.

Secondary: To evaluate safety (AE/SAE incidence, severity), total steroid dose and duration, and changes in 6-minute walk distance (6MWD), modified Medical Research Council dyspnea scale (mMRC), St George's Respiratory Questionnaire (SGRQ), and Leicester Cough Questionnaire (LCQ).

Exploratory: To analyze the relationship between treatment response and changes in T-cell subsets, inflammatory cytokines (IL-1 beta, IL-6, IL-10), KL-6, ALC, CD4+ Th1/Th17, Tregs, NLR, AEC, and gut microbiome.

STUDY DESIGN:

Sixty eligible participants will be randomized 1:1 to:

* Experimental arm: Spirulina-Bifidobacterium capsules 1080 mg twice daily orally, fish oil-grape seed-blueberry soft capsules 1200 mg twice daily orally, and Ganoderma spore oil 800 mg twice daily orally, plus methylprednisolone (dose and tapering per investigator assessment, referencing NCCN Guidelines 2025 v1). * Control arm: Matching placebo orally plus methylprednisolone (per NCCN Guidelines 2025 v1), tapered until symptoms and imaging improve and then discontinued.

Pneumonitis imaging (chest X-ray or CT) will be assessed at baseline and on Days 3, 7, 14, 28, 42, and 56, and at 2-3 months post-treatment, with additional imaging as clinically indicated. Pneumonitis grade will be determined by an Independent Radiologic Review Committee (IRRC) blinded to treatment allocation.

PARTICIPANTS:

Adults 18-75 years of age with histologically or cytologically confirmed malignancy, who have received at least one cycle of immune checkpoint inhibitor therapy, and who develop Grade 3-4 CIP per CTCAE v5.0 and radiologic grading.

FOLLOW-UP:

All participants will be followed for 2 years or until death, with contacts every 90 (plus or minus 7) days.

Вмешательства

• Пищевая добавка Spirulina-Bifidobacterium capsule
  1080 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.
• Пищевая добавка Fish oil-grape seed-blueberry soft capsule
  1200 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.
• Пищевая добавка Ganoderma spore oil
  800 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.
• Препарат Methylprednisolone
  Dose and tapering schedule per investigator assessment, referencing NCCN Guidelines 2025 version 1 for immune-related pneumonitis, continued until clinical and radiologic improvement and then tapered to discontinuation.
• Другое Matching placebo
  Oral placebo capsules identical in appearance, color, shape, size, odor, taste, packaging, label, route, and dosing frequency to the investigational nutritional products, administered to maintain blinding and control for non-specific effects.

Первичные конечные точки

• Time to immune-related pneumonitis downgrading [Срок оценки: From randomization until first IRRC-confirmed pneumonitis grade reduction of at least 1 grade, assessed up to 6 months]
• Proportion of participants with pneumonitis downgrading at 3 months [Срок оценки: 3 months (plus or minus 7 days) after randomization]

Вторичные конечные точки (7)

• Change from baseline in 6-minute walk distance (6MWD) [Срок оценки: Baseline, Day 28, Day 56, Month 2-3]
• Change from baseline in modified Medical Research Council (mMRC) dyspnea scale [Срок оценки: Baseline, Day 28, Day 56, Month 2-3]
• Change from baseline in St George's Respiratory Questionnaire (SGRQ) total score [Срок оценки: Baseline, Day 28, Day 56, Month 2-3]
• Change from baseline in Leicester Cough Questionnaire (LCQ) score [Срок оценки: Baseline, Day 28, Day 56, Month 2-3]
• Total cumulative corticosteroid dose [Срок оценки: From randomization to end of corticosteroid treatment, up to approximately 6 months]
• Duration of corticosteroid treatment [Срок оценки: From randomization to end of corticosteroid treatment, up to approximately 6 months]
• Incidence of adverse events, treatment-related adverse events, and serious adverse events [Срок оценки: From randomization through 30 days after last dose; SAEs collected through 90 days after last dose]

Критерии участия

Критерии включения

• Voluntary participation with full understanding of the study and signed informed consent form.
• Age 18 to 75 years (inclusive) on the day of informed consent signing.
• Histologically or cytologically confirmed malignancy.
• Received at least one cycle of immune checkpoint inhibitor therapy.
• Grade 3-4 immune-related pneumonitis (per CTCAE v5.0 and radiologic grading).
• ECOG performance status 0-2, with expected survival of more than 3 months.
• Adequate organ function based on laboratory results (without transfusion, apheresis, erythropoietin, or granulocyte colony-stimulating factor support within 14 days before the first dose). Women of childbearing potential must have a negative serum pregnancy test within 7 days before first dose.

Критерии исключения

• Severe cardiac, cerebrovascular, renal, hematologic, or other serious systemic disease, including: NYHA Class III-IV heart failure; acute myocardial infarction or unstable angina within 6 months; severe post-stroke functional impairment (mRS greater than or equal to 3); progressive neurodegenerative disease; Child-Pugh Class B or C liver disease or acute liver failure; CKD stage 4-5 (eGFR less than 30 mL/min/1.73 m2) or requiring dialysis; absolute neutrophil count less than 1.5 x 10\^9/L, platelet count less than 50 x 10\^9/L, or Grade 3 or higher anemia (Hb less than 8 g/dL).
• Severe allergic constitution or contraindications to the study treatment.
• Significant psychiatric or psychological disorder, or doubts about the treatment plan.
• Investigator judgment that the patient is unsuitable for the trial (e.g., poor follow-up adherence, refusal of supportive care).
• Use of anti-tumor traditional Chinese medicine within 14 days before first dose.
• History of or active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• Severe acute or chronic infection.
• Known alcohol or drug abuse history.
• Pregnancy or breastfeeding.
• Use of antibiotics, probiotic food, or microecological preparations within 2 weeks before enrollment.
• Prior treatment-related lung injury: (a) targeted-therapy-related pulmonary toxicity (prior EGFR-TKI, ALK inhibitor, VEGF inhibitor, or antibody-drug conjugate causing interstitial lung disease or pneumonitis that has not fully resolved, with radiologic fibrosis or persistent functional impairment); (b) thoracic radiation-related lung injury (radiation pneumonitis or radiation fibrosis with irreversible CT findings).
• Use of another investigational drug within 28 days before first dose that, per investigator judgment, would interfere with evaluation of study treatment.
• Gastrointestinal disorder precluding oral administration.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Guangzhou Medical University, Department of Pulmonary Onc — Гуанчжоу

Идентификаторы

NCT: NCT07554885 · CROC-Edinburgh001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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