Gut Microbiome and Its Immune Modulation in Locally Advanced Rectal Cancer

NCT ID: NCT05079503

Last Updated: 2021-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-15

Study Completion Date

2024-01-30

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Locally Advanced Rectal Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single arm study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TNT plus GEN-001

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.

Group Type EXPERIMENTAL

GEN-001

Intervention Type 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.

Interventions

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GEN-001

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.

Intervention Type DRUG

Other Intervention Names

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Lactococcus lactis

Eligibility Criteria

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Inclusion Criteria

1. Age \> 19 years
2. Locally advanced rectal cancer, histologically confirmed; clinically T3/4, clinically N+, enlarged lateral lymph nodes, extramural vascular invasion (+), or mesorectal fascia (+)
3. 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)
4. Patients with ability to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities that may alter absorprtion
5. Patients with ability to collect their blood and stool samples

Exclusion Criteria

1. Rectal cancer, other histologic type than adenocarcinoma (such as squamous cell carcinoma)
2. Patients who schedule to receive concurrent chemoradiotherapy or short-course radiotherapy alone followed by surgery and adjuvant chemotherapy
3. Patients who need emergent surgery or colostomy due to obstruction or bleeding
4. Prior use of proton pump inhibitors or H2 blockers, probiotics, immunosuppressive agents, and antibiotics within 4 weeks
5. Patients have concurrent medication that may interact with fluoropyrimidine or oxaliplatin (i.e. flucytosine, phenytoin, or warfarin)
6. Known prior history of severe adverse events during fluoropyrimidine or deficiency of dihydropyrimidine dehydrogenase (DPD)
7. Known prior severe hypersensitivity to platinum
8. Patients who have an active infection requiring antibiotics, antifungal, or antiviral agents
9. Prior solid organ or allogenic stem cell transplantation

11\. 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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Korean Cancer Study Group

OTHER

Sponsor Role lead

Responsible Party

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SoohyeonLee

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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

Role: CONTACT

+82-2-920-5690

Jwa Hoon Kim, M.D.

Role: CONTACT

+82-2-2199-3804

Other Identifiers

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2021AN0403

Identifier Type: -

Identifier Source: org_study_id