To investigate dynamic change of gut microbiomes and metabolites, and their effects on immune modulation. To evaluate the efficacy and safety of TNT with GEN-001 (Lactococcus lactis) and identify predictive biomarkers for pathologic response in patients with locally advanced rectal cancer (LARC).
The multimodality strategy, neoadjuvant chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT) followed by surgery, has been widely used to improve local control and overall survival in locally advanced rectal cancer (LARC). TNT is a recently promising strategy incorporating systemic chemotherapy following short-course radiotherapy before surgery in LARC, and showed superior rates of pathologic complete response (pCR) compared with the concurrent CRT followed by surgery and adjuvant chemotherapy (CRT-A). However, issues regarding neoadjuvant therapy-related toxicity as well as disease progression during TNT have been raised, which need to identify biomarkers for prediction of treatment responses and safety in patients with LARC. Growing evidence suggests that gut microbiomes interact with tumor microenvironment and are related with inflammation and immunomodulation. The association between gut microbiomes and responses of chemotherapy or immunotherapy has been previously reported. The administration of certain beneficial microbiome can be one of the strategies to treat gut dysbiosis in cancer patients, restoring microbial diversity and changing the composition of microbiome. GEN-001, Lactobacillus lactis is a live, purified facultative anaerobic gram-positive probiotic lactic acid bacterial strain. The preclinical studies showed the potential therapeutic effects of GEN-001 as an anti-cancer treatment through the activation of immune cells, including CD4 or CD8 T-cells and natural killer cells, and synergistic effects with oxaliplatin chemotherapy. Therefore, the investigators plan to investigate dynamics of gut microbiomes and metabolites, and their effects on immune modulation. Additionally investigators plan to evaluate the efficacy and safety of TNT with GEN-001 and identify predictive biomarkers for pathologic response in patients with LARC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
GEN-001, Lactobacillus lactis is a live, purified facultative anaerobic gram-positive probiotic lactic acid bacterial strain. GEN-001 is orally administered once daily during total TNT periods.
Dynamic change of gut microbiome: a-diversity index
16s rRNA sequencing
Time frame: up to 30 weeks
Dynamic change of gut microbiome: b-diversity index
16s rRNA sequencing
Time frame: up to 30 weeks
Immune modulation in blood
Cytotoxic T cells or regulatory T cells using flowcytometry
Time frame: up to 30 weeks
Immune modulation in tissue
CD4 or CD8 tumor-infiltrating lymphocytes using immunohistochemistry
Time frame: up to 30 weeks
Efficacy and safety of TNT plus GEN-001
Achieving pathologic complete response
Time frame: up to 30 weeks
Identify predictive biomarkers for pathologic responders
Prediction for pathologic complete response
Time frame: up to 30 weeks
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