Gut Microbiome and Its Immune Modulation in Locally Advanced Rectal Cancer

NCT05079503 | Unknown

• 1 other identifier: 2021AN0403
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Locally Advanced Rectal Cancer

Outcome Measures

Primary Outcomes (4)

• Dynamic change of gut microbiome: a-diversity index

  16s rRNA sequencing

  up to 30 weeks

• Dynamic change of gut microbiome: b-diversity index

  16s rRNA sequencing

  up to 30 weeks

• Immune modulation in blood

  Cytotoxic T cells or regulatory T cells using flowcytometry

  up to 30 weeks

• Immune modulation in tissue

  CD4 or CD8 tumor-infiltrating lymphocytes using immunohistochemistry

  up to 30 weeks

Secondary Outcomes (2)

• Efficacy and safety of TNT plus GEN-001

  up to 30 weeks

• Identify predictive biomarkers for pathologic responders

  up to 30 weeks

Study Arms (1)

TNT plus GEN-001

EXPERIMENTAL

Total neoadjuvant therapy (TNT) includes short-course radiotherapy (25 Gy/5fx), followed by systemic chemotherapy with FOLFOX regimen for 3-6 months. GEN-001 is orally administered once daily during total TNT periods and surgery will be performed 1 month after systemic chemotherapy.

Drug: GEN-001

Interventions

GEN-001 DRUG

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.

Also known as: Lactococcus lactis

TNT plus GEN-001

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 19 years
• Locally advanced rectal cancer, histologically confirmed; clinically T3/4, clinically N+, enlarged lateral lymph nodes, extramural vascular invasion (+), or mesorectal fascia (+)
• Patients who schedule to receive total neoadjuvant therapy, including short-course radiotherapy (25 Gy in 5 fractions), followed by FOLFOX chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin)
• Patients with ability to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities that may alter absorprtion
• Patients with ability to collect their blood and stool samples

You may not qualify if:

• Rectal cancer, other histologic type than adenocarcinoma (such as squamous cell carcinoma)
• Patients who schedule to receive concurrent chemoradiotherapy or short-course radiotherapy alone followed by surgery and adjuvant chemotherapy
• Patients who need emergent surgery or colostomy due to obstruction or bleeding
• Prior use of proton pump inhibitors or H2 blockers, probiotics, immunosuppressive agents, and antibiotics within 4 weeks
• Patients have concurrent medication that may interact with fluoropyrimidine or oxaliplatin (i.e. flucytosine, phenytoin, or warfarin)
• Known prior history of severe adverse events during fluoropyrimidine or deficiency of dihydropyrimidine dehydrogenase (DPD)
• Known prior severe hypersensitivity to platinum
• Patients who have an active infection requiring antibiotics, antifungal, or antiviral agents
• Prior solid organ or allogenic stem cell transplantation
• \. Patients who have clinically significant medical disease
• Cardiovascular disease \<6 months prior to enrollment (myocardial infarction, unstable angina, coronary artery bypass surgery or percutaneous coronary intervention)
• Cerebral vascular accident/stroke (\<6 months prior to enrollment)
• Congestive heart failure (≥New York Heart Association (NYHA) Classification Class II)
• Uncontrolled hypertension by standard therapy: systolic blood pressure \>160 mmHg or diastolic blood pressure \> 100 mmHg
• Serious cardiac arrhythmia requiring medication 12. Pregnant women 13. Patients who have psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with study requirements

Sponsors & Collaborators

• Korean Cancer Study Group: lead

Central Study Contacts

Soohyeon Lee, M.D., Ph.D.

CONTACT

+82-2-920-5690; soohyeon_lee@korea.ac.kr

Jwa Hoon Kim, M.D.

CONTACT

+82-2-2199-3804; jhoonkim@korea.ac.kr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Single arm study

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: October 15, 2021
• Study Start: December 15, 2021
• Primary Completion: August 30, 2023
• Study Completion: January 30, 2024
• Last Updated: October 15, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share