Effects of synbiotics supplementation on chronological change of gut microbiome and cancer immunotherapy in Treatment-naive non-small cell lung cancer patients: a double-blind randomized controlled study (SYNCOPATION study)
SYNCOPATION study
Shoji Fumihiro
Shiga University Of Medical Science Hospital
Seta Tsukinowa cho, Otsu, Shiga
+81-77-548-2245
fumshoji@belle.shiga-med.ac.jp
Shoji Fumihiro
Shiga University Of Medical Science Hospital
Seta Tsukinowa cho, Otsu, Shiga
+81-77-548-2245
fumshoji@belle.shiga-med.ac.jp
Recruiting
Feb. 10, 2023
May. 15, 2023
60
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
1) Patients with histologically or cytologically diagnosed Stage IV (T any, N any, M1a or M1b or M1c (UICC 8th)) non-small cell lung cancer or postoperative recurrence not eligible for radical therapy.
PD-L1 protein expression and histology (squamous or non-squamous) are not required.
2) Patients not eligible for epidermal growth factor receptor (EGFR) inhibitors, anaplastic lymphoma kinase (ALK) inhibitors, or c-ros oncogene (ROS1) inhibitors.
3) Patients scheduled to receive either pembrolizumab monotherapy or the following pembrolizumab combination therapy
Pembrolizumab monotherapy: PD-L1 positive (Tumor Proportion Score (TPS)>= 50% (strongly positive))
Pembrolizumab + pemetrexed + cisplatin/ carboplatin: non-squamous non-small cell lung cancer
Pembrolizumab + nab-Paclitaxel/paclitaxel + carboplatin: Squamous cell non-small cell lung cancer
4) Patients with at least one measurable lesion based on RECIST version 1.1 on imaging test within 28 days prior to enrollment.
However, bone lesions, cystic lesions, and lesions with a history of topical treatment such as radiotherapy are considered as non-measurable lesions.
5) Patients untreated with chemotherapy including molecular-targeted drugs and cancer immunotherapy.
However, a history of preoperative/postoperative adjuvant therapy is acceptable if completed at least 6 months prior to the date of enrollment.
6) Patients deemed able to cooperate in the collection and submission of fecal specimens and recording of patient diaries.
7) Patients who can orally ingest synbiotic foods (synprotec or placebo food).
8) Patients who are at least 20 years of age at the time of consent
9) Patients expected to survive more than 3 months
10) Patients with ECOG Performance Status 0 or 1
11) Patients who meet the following criteria for major organ function within 14 days prior to enrollment (based on the date of enrollment, the same day of prior two weeks is acceptable).
If there are multiple test results within the period, the latest one will be used.
Test item Reference value
Neutrophil count >=1,500/mm3
Platelet count >=100,000 / mm3
Hemoglobin >=9.0 g/dL or >=5.6 mmol/L (after 4 weeks of transfusion)
AST/ALT =<2.5 x ULN (if liver metastases present=<5.0 x ULN)
Total bilirubin =<1.5 x ULN
Creatinine =<1.5 x ULN
If creatinine >1.5 x ULN, if creatinine clearance >= 60 mL/min
12) Patients who have been fully informed of the contents of this study and have given their written consent.
1) Patients who are taking medicines containing prebiotics and probiotics on a daily basis, or taking supplements (including synprotec) at the time of informed consent.
2) Patients who are allergic to galactooligosaccharides or milk.
3) Patients with active infection of HIV, HBV, HCV, or syphilis.
However, the following are acceptable for enrollment
HBV: Patients who are HBs antibody-positive, HBc antibody-positive, or HBs antigen-positive, but whose viral load is less than sensitivity and who have inactive hepatitis may be enrolled.
HCV: Antibody-positive patients with inactive hepatitis may be enrolled.4) Patients participating in other clinical trials or clinical studies.
5) Patients who have received radiation therapy to the lungs exceeding 30 Gy within 4 weeks of the date of consent.
6) Patients who completed palliative radiation therapy within 7 days prior to enrollment in this study.
7) Patients who have received a live vaccine within 30 days prior to enrollment in this study.
8) Patients with clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or carcinomatosis.
9) Patients with a history of malignancy other than non-small cell lung cancer, except for those who have been relapse-free for 5 years after the start of curative treatment.
10) Patients with active central nervous system (CNS) metastases or cancerous meningitis. However, patients who are asymptomatic and clinically stable may be enrolled.
11) Patients with a history of severe hypersensitivity reactions to other monoclonal antibodies.
12) Patients with hypersensitivity to cisplatin, carboplatin, pemetrexed, nab-paclitaxel and paclitaxel.
13) Patients with Grade >=2 peripheral neuropathy according to CTCAE version 5.0.
14) Patients with active autoimmune disease requiring systemic treatment within the past 2 years.
15) Patients chronically taking systemic steroids.
16) Patients with psychiatric, dementia, or substance abuse disorders that have been determined to have the potential to affect their participation in this study.
17) Patients with ascites or pleural effusions requiring treatment. However, patients who are clinically stable with treatment may be eligible for enrollment.
18) Patients with complication of interstitial lung disease or a history of pnemonitis requiring oral/intravenous corticosteroid therapy.
19) Pregnant patients, lactating patients, or patients who wish to have their own or their partner pregnancy during the period of this study.
20) Other patients who are judged by the principal investigator or sub-investigator to be inappropriate to participate in this study.
20age old over
No limit
Both
non-small Cell Lung Cancer
Monotherapy: pembrolizumab + synbiotics*
Non-squamous cell carcinoma: (Induction therapy: 4 courses) Pembrolizumab + pemetrexed + cisplatin or carboplatin + synbiotics*
(maintenance therapy) pembrolizumab + pemetrexed + synbiotics*
Squamous cell carcinoma: (Induction therapy: 4 courses) Pembrolizumab + paclitaxel or nab-paclitaxel + carboplatin + synbiotics*
(maintenance therapy) Pembrolizumab + synbiotics*
*take 3 times a day for 52 weeks
Gut microbiome change index
Change in bifidobacteria count from baseline to 24 +-4 weeks from the start date of cancer immune combination therapy
Gut microbiome change index
Bifidobacteria count
Composition of intestinal bacteria, alpha diversity, number of bacteria, pH, organic acid concentration
Immuno-nutritional index
prognostic nutritional index
controlling nutritional risk score
geriatric nutritional risk index
Diversity of T cell antigen receptors in peripheral blood (TCR repertoire)
Anti-tumor efficacy endpoints
Response rate, disease control rate
Progression-free survival
Safety endpoints
Adverse event rate
Yakult Honsha Co.,Ltd.
Not applicable
Clinical Research Network Fukuoka Certified Review Board
