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

N/ANot Yet RecruitingNCT07554885

Guangzhou Institute of Respiratory Disease60 enrolled

Overview

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.

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.

Interventions

Spirulina-Bifidobacterium capsuleDIETARY_SUPPLEMENT

1080 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.

Fish oil-grape seed-blueberry soft capsuleDIETARY_SUPPLEMENT

1200 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.

Ganoderma spore oilDIETARY_SUPPLEMENT

800 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.

MethylprednisoloneDRUG

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.

Matching placeboOTHER

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Voluntary participation with full understanding of the study and signed informed consent form. 2. Age 18 to 75 years (inclusive) on the day of informed consent signing. 3. Histologically or cytologically confirmed malignancy. 4. Received at least one cycle of immune checkpoint inhibitor therapy. 5. Grade 3-4 immune-related pneumonitis (per CTCAE v5.0 and radiologic grading). 6. ECOG performance status 0-2, with expected survival of more than 3 months. 7. 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. Exclusion Criteria: 1. 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). 2. Severe allergic constitution or contraindications to the study treatment. 3. Significant psychiatric or psychological disorder, or doubts about the treatment plan. 4. Investigator judgment that the patient is unsuitable for the trial (e.g., poor follow-up adherence, refusal of supportive care). 5. Use of anti-tumor traditional Chinese medicine within 14 days before first dose. 6. History of or active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). 7. Severe acute or chronic infection. 8. Known alcohol or drug abuse history. 9. Pregnancy or breastfeeding. 10. Use of antibiotics, probiotic food, or microecological preparations within 2 weeks before enrollment. 11. 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). 12. Use of another investigational drug within 28 days before first dose that, per investigator judgment, would interfere with evaluation of study treatment. 13. Gastrointestinal disorder precluding oral administration.

Outcomes

Primary Outcomes

Time to immune-related pneumonitis downgrading

Time from randomization to the first imaging assessment, confirmed by the Independent Radiologic Review Committee, showing a reduction of at least 1 grade in pneumonitis severity compared with baseline, per CTCAE v5.0 and radiologic grading.

Time frame: 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

Proportion of participants in each arm with an IRRC-confirmed reduction of at least 1 pneumonitis grade from baseline within 3 months after randomization.

Time frame: 3 months (plus or minus 7 days) after randomization

Secondary Outcomes

Change from baseline in 6-minute walk distance (6MWD)

Distance (meters) walked in 6 minutes on a flat, hard surface, measured according to a standardized protocol by trained personnel.

Time frame: Baseline, Day 28, Day 56, Month 2-3

Change from baseline in modified Medical Research Council (mMRC) dyspnea scale

Self-reported dyspnea severity on the 0-4 mMRC scale, where 0 indicates no dyspnea except with strenuous exercise and 4 indicates dyspnea too severe to leave the house.

Time frame: Baseline, Day 28, Day 56, Month 2-3

Change from baseline in St George's Respiratory Questionnaire (SGRQ) total score

Validated Chinese version of SGRQ; total score ranges 0-100, higher scores indicate worse respiratory-related quality of life.

Time frame: Baseline, Day 28, Day 56, Month 2-3

Change from baseline in Leicester Cough Questionnaire (LCQ) score

Validated Chinese version of LCQ; total score ranges 3-21, higher scores indicate better cough-related quality of life.

Time frame: Baseline, Day 28, Day 56, Month 2-3

Total cumulative corticosteroid dose

Total cumulative glucocorticoid dose used for CIP, expressed in methylprednisolone-equivalent milligrams.

Time frame: From randomization to end of corticosteroid treatment, up to approximately 6 months

Duration of corticosteroid treatment

Total number of days on glucocorticoid therapy for CIP, from initiation to final discontinuation.

Time frame: From randomization to end of corticosteroid treatment, up to approximately 6 months

Incidence of adverse events, treatment-related adverse events, and serious adverse events

Incidence, severity (CTCAE v5.0), and relationship to study treatment of all AEs, TRAEs, and SAEs.

Time frame: From randomization through 30 days after last dose; SAEs collected through 90 days after last dose

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts