Locally Advanced Rectal CancerNCT05079503
Gut Microbiome and Its Immune Modulation in Locally Advanced Rectal Cancer
A study testing GEN-001 in people with Locally Advanced Rectal Cancer, run by Korean Cancer Study Group.
Trial 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). Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer
- What is being tested?
- GEN-001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 15 Dec 2021to 30 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Efficacy and Safety of GEN-001 (Lactococcus Lactis) Plus Total Neoadjuvant Therapy and Dynamic Change of Gut Microbiome in Locally Advanced Rectal Cancer : Exploratory, Pilot, Prospective, Longitudinal Study
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).
Read the detailed description
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
- Locally Advanced Rectal Cancer
- Being tested
- GEN-001
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEN-001Drug
Also called Lactococcus lactis
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: GEN-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dynamic change of gut microbiome: a-diversity index
16s rRNA sequencing
Measured: up to 30 weeks
Dynamic change of gut microbiome: b-diversity index
16s rRNA sequencing
Measured: up to 30 weeks
Immune modulation in blood
Cytotoxic T cells or regulatory T cells using flowcytometry
Measured: up to 30 weeks
Immune modulation in tissue
CD4 or CD8 tumor-infiltrating lymphocytes using immunohistochemistry
Measured: up to 30 weeks
Secondary outcomes (2)
Efficacy and safety of TNT plus GEN-001
Achieving pathologic complete response
Measured: up to 30 weeks
Identify predictive biomarkers for pathologic responders
Prediction for pathologic complete response
Measured: up to 30 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2021
- Study start15 Dec 2021 (estimated)
- Primary completion30 Aug 2023 (estimated)
- Study completion30 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm study
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Korean Cancer Study Group
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, SoohyeonLee, Korea University Anam Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05079503
- Sponsor's protocol ID
- 2021AN0403
- Status last verified
- Oct 2021
- First submitted
- 14 Sep 2021
- Last updated
- 15 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of GEN-001 (Lactococcus Lactis) Plus Total Neoadjuvant Therapy and Dynamic Change of Gut Microbiome in Locally Advanced Rectal Cancer : Exploratory, Pilot, Prospective, Longitudinal Study
- ClinicalTrials.gov ID
- NCT05079503
- Acronym / sponsor ID
- 2021AN0403
- Conditions
- Locally Advanced Rectal Cancer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Korean Cancer Study GroupUniversity, hospital or other
- Study start
- 15 Dec 2021 (estimated)
- Primary completion
- 30 Aug 2023 (estimated)
- Study completion
- 30 Jan 2024 (estimated)
- First posted
- 15 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm study
| Arm | Type | Receives |
|---|---|---|
| TNT plus GEN-001 | Experimental | Drug: GEN-001Total 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GEN-001Also: Lactococcus lactisGEN-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. | Drug | TNT plus GEN-001 |
Primary outcome
Dynamic change of gut microbiome: a-diversity index
Time frame: up to 30 weeks
16s rRNA sequencing
Dynamic change of gut microbiome: b-diversity index
Time frame: up to 30 weeks
16s rRNA sequencing
Immune modulation in blood
Time frame: up to 30 weeks
Cytotoxic T cells or regulatory T cells using flowcytometry
Immune modulation in tissue
Time frame: up to 30 weeks
CD4 or CD8 tumor-infiltrating lymphocytes using immunohistochemistry
2 secondary outcomes
Efficacy and safety of TNT plus GEN-001
Time frame: up to 30 weeks
Identify predictive biomarkers for pathologic responders
Time frame: up to 30 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A study testing GEN-001 in people with Locally Advanced Rectal Cancer, run by Korean Cancer Study Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Soohyeon Lee, M.D., Ph.D. (+82-2-920-5690, soohyeon_lee@korea.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dynamic change of gut microbiome: a-diversity index (time frame: up to 30 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2021.