Prospective Randomized Controlled Trial to Evaluate the Effect of Adding Clostridium butyricum MIYAIRI 588 to Preoperative Adjuvant Chemotherapy with Immuno checkpoint inhibitor for Non-Small Cell Lung Cancer

JRCT ID: jRCTs031240597

Registered date:08/01/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patients who receive neoadjuvant chemotherapy with immune checkpoint inhibitors for NSCLC
• Date of first enrollment: 08/01/2025
• Target sample size: 24
• Study type: Interventional
• Intervention(s): Adding clostridium butyricum miyairi to neoadjuvant chemotherapy with immune checkpoint inhibitor.

Outcome(s)

• Primary Outcome: No primary endpoint is established, because this is an exploratory study.

Secondary Outcome

1) Major Pathological Response
2) Pathological Complete Response
3) Overall Response Rate
4) Disease Control Rate
5) Number of CD8-positive T cells in the resected lung
6) Percentage of CD8-positive T cells in the leukocytes of the resected lung
7) Tumor-infiltrating lymphocyte score in the resected lung
8) Change in the ratio of CD4/CD8-positive T cells between before and 4-12 weeks after the start of chemoimmunotherapy
9) Change in total lymphocyte count (TLC) between before and 4-12 weeks after the start of chemoimmunotherapy
10) Change in the prognostic nutritional index (PNI) between before and 4-12 weeks after the start of chemoimmunotherapy
11) Change in the neutrophil/lymphocyte ratio (NLR) between before and 4-12 weeks after the start of chemoimmunotherapy
12) Change in platelet/lymphocyte ratio (PLR) between before and 4-12 weeks after the start of chemoimmunotherapy
13) Change in lymphocyte/monocyte ratio (LMR) between before and 4-12 weeks after the start of chemoimmunotherapy
14) Change in Glasgow Prognostic Score (GPS) between before and 4-12 weeks after the start of chemoimmunotherapy
15) Change in Systemic Immune-Inflammation Index (SII) between before and 4-12 weeks after the start of chemoimmunotherapy
16) Changes in gut microbiome between before and 4-12 weeks after the start of chemoimmunotherapy

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

Patients who meet all of the following conditions are eligible for the study.
1) Adults aged 18 to 80 years at the time of obtaining consent.
2) ECOG performance status (PS) of 0-2.
3) Main organ functions are maintained.
4) Patients with resectable stage II to IIIB non-small cell lung cancer.
5) Patients who are not eligible for epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors.
6) Patients who are scheduled to receive one of the following combination chemotherapy regimens with immune checkpoint inhibitors.
For patients with non-squamous non-small cell lung cancer
Nivolumab, pemetrexed, cisplatin or Keytruda, pemetrexed, cisplatin
For patients with squamous cell non-small cell lung cancer
Nivolumab, paclitaxel, carboplatin or Keytruda, gemcitabine, cisplatin
7) Patients with measurable lesions based on RECIST version 1.1. However, bone lesions, cystic lesions, and lesions that have undergone local treatment such as radiotherapy are considered unmeasurable lesions.
8) Patients who have not received chemotherapy or cancer immunotherapy, including molecular-targeted drugs. However, patients who have received preoperative/postoperative adjuvant therapy are allowed if the treatment was completed within 6 months of the registration date.
9) Patients who are judged to be able to cooperate with the collection and submission of stool samples and the patient diary (stool collection date, food intake status, and history of antibiotic administration, etc.).
10) Patients who have been fully informed of the details of this study and have given their written consent freely and of their own accord after fully understanding the details.

Exclude criteria

Patients who meet any of the following conditions are not eligible.
1) Patients with a history of hypersensitivity to immunotherapy or any component of Bacillus butyrate preparations.
2) Patients who are taking Bacillus butyrate preparations (including supplements) (however, those who can wash out the Bacillus butyrate preparations for at least 5 days between the date of consent and the start of study drug administration will not be excluded).
3) Patients who have received radiation therapy to the lungs exceeding 30 Gy within 4 weeks of the date of obtaining consent.
4) Patients who have completed palliative radiation therapy within 7 days prior to enrollment in this study.
5) Patients who received a live vaccine within 30 days prior to enrollment in this study.
6) Patients who received antibiotic therapy within 30 days prior to enrollment in this study.
7) Patients with clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or carcinomatosis.
8) Patients with a history of malignancy other than non-small cell lung cancer. 8) Patients with a history of malignancy other than non-small cell lung cancer, except for patients who have been free of recurrence for 5 years after the start of curative treatment.
9) Patients with active central nervous system (CNS) metastases or cancerous meningitis, but may be enrolled if asymptomatic and clinically stable.
10) Patients with peripheral neuropathy (Grade 2 or more, according to CTCAE version 5.0).
11) Patients with active autoimmune disease requiring systemic treatment within the past 2 years.
12) Patients who are taking systemic steroids on a continuous basis.
13) Patients with psychiatric, dementia, or substance abuse disorders that have been determined to have the potential to affect their participation in this study.
14) Patients with ascites or pleural effusion requiring treatment. However, patients who are clinically stable with treatment may be eligible for inclusion.
15) Patients with interstitial lung disease or a history of pulmonary inflammation requiring oral/intravenous corticosteroid therapy.
16) Patients with dementia or other conditions requiring substitution.
17) Patients who are pregnant, possibly pregnant, within 28 days postpartum, or lactating.
18) Other patients who are judged by the principal investigator or subinvestigator to be inappropriate for the safe conduct of this study.

Related Information

• Primary Sponsor: Suzuki Hidemi
• Source(s) of Monetary Support: Chiba University Hospital