Hepatocellular CarcinomaPhase 2MOTHERNCT06551272
Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma
A Phase 2 study testing EXL01 in people with Hepatocellular Carcinoma, run by Center Eugene Marquis at 6 sites in France.
Trial summary
Hepatocellular carcinoma (HCC) is the most common liver primary cancer with a high rate of mortality. Since the results of IMbrave150, immunotherapy have emerged as a standard of care for HCC patients advanced and/or unresectable in first line of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- EXL01
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 6 sitesFrance
- Study dates
- 12 Mar 2025to 12 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and Female
- Age ≥18 years at time of signing informed consent
- Presenting with HCC, diagnosed either by histological or radiological criteria as described by EASL
- Locally advanced or metastatic and/or unresectable HCC according a Multidisciplinary Team meeting
- Progressive disease after exposure to standard-of-care approved first-line immunotherapy
- Decision made by the physician to continue the same standard-of-care approved first-line immunotherapy beyond progression
Show all 11Show fewer
- Child-Pugh A within 7 days prior to inclusion
- ECOG performance status 0 to 1
- Adequate hematological (Hemoglobin >8.5g/dL, platelets >60G/L, neutrophils >1.5G/L) and renal (creatinine clearance > 50 mL/min according to Cockcroft or MDRD formula) functions
- Disease measurable by RECIST 1.1
- Signed written Informed consent
Who cannot join
- Partial response achieved under standard-of-care approved first-line immunotherapy
- CTCAE Grade ≥3 or more toxicity under standard-of-care approved first-line immunotherapy, or persistent toxicity Grade >1
- Liver involvement > 50%
- Presence of major macro vascular invasion (except Vp1/Vp2)
- Pregnant woman, or breastfeeding or women of child-bearing potential with no adequate contraception (see §4.3.1)
- Under curatorship, guardianship, safeguard of justice or deprived of liberty
Show all 31Show fewer
- History of serious autoimmune disease
- Interstitial lung disease
- HBV chronic infection with HBV DNA > 100 IU/mL or without antiviral therapy; HBV patients with cirrhosis should be treated
- HIV infection
- Immunosuppression, including subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent)
- Transplanted liver, or patient with intent for transplantation
- Has difficulties in swallowing.
- Has undergone major surgery or significant trauma ≤4 weeks prior to Screening. Note: Participants who had surgery >4 weeks prior to Screening must have recovered adequately from any toxicity and/or complications from the surgery or trauma prior to starting study intervention.
- Is currently participating in or has participated in a study with an investigational compound or device within 3 months prior to the first dose of study intervention.
- Note: Participants who have entered the follow-up phase of an investigational study may participate so long as it has been at least 3 months since the last dose of the previous investigational agent.
- Has a systemic infection or other serious infection requiring systemic treatment within 30 days prior to Screening.
- Has a history of hypersensitivity to EXL01 and/or any excipients, which are listed in the IB, and/or to soybean or soy-containing products
- Has a history of hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
- Active inflammatory intestinal disease (Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea, or other inflammatory disease requiring anti-inflammatory medications
- Current probiotics administration, or planned probiotics administration during treatment course.
- Specific contra-indication to the continuation of the standard-of-care approved first-line immunotherapy :
- 21.1: for atezolizumab-bevacizumab:
- Thromboembolic events in the 3 months prior to inclusion
- Prior bleeding event due to untreated or incompletely treated esophageal and / or gastric varices within 6 months' prior inclusion
- Has a history of hypersensitivity to the atezolizumab or to any of the excipients listed in section 6.1 of the SmPC of atezolizumab
- Has a history of hypersensitivity to bevacizumab or to any of the excipients listed in section 6.1 of the SmPC of bevacizumab
- Uncontrolled hypertension
- Clinically significant cardiovascular disease such as pre-existing coronary artery disease, or congestive heart failure
- Proteinuria 21.2: for durvalumab:
- Has a history of hypersensitivity to the durvalumab or to any of the excipients listed in section 6.1 of the SmPC of durvalumab.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Marion TROCHET contact
6 sites in 1 country
France6 sites, 2 recruiting
- Active, not recruiting
hôpital Avicenne
Bobigny, 93000
- Active, not recruiting
CHU de Bordeaux
Bordeaux
- Recruiting
Hôpital Beaujon
Clichy, 92100
Mohamed BOUATTOUR, 0140875614, mohamed.bouattour@aphp.fr
Mohamed BOUATTOUR, Dr
- Active, not recruiting
CHU de Nantes Hotel Dieu
Nantes, 44 000
- Recruiting
Centre de luttre contre le cancer Eugène Marquis
Rennes, 35000
Héloise BOURIEN, 0299253296, h.bourien@rennes.unicancer.fr
Héloise BOURIEN, DR
- Active, not recruiting
Gustave ROUSSY
Villejuif, 94805
About this study
Hepatocellular carcinoma (HCC) is the most common liver primary cancer with a high rate of mortality. Since the results of IMbrave150, immunotherapy have emerged as a standard of care for HCC patients advanced and/or unresectable in first line of treatment. The objective response rate was about 30%, but half of patients would present only stable disease and about 20% progressive disease.
Faecalibacterium prausnitzii is one of the most abundant bacterial in human gut microbiota, around 5% of total bacteria in feces.
Read more
For patients with metastatic melanoma, treated with ipilimumab, an antibody targeting CTLA-4 (Cytotoxic T-lymphocyte-associated antigen 4), patients with a baseline gut microbiota enriched with Faecalibacterium had a significantly better clinical outcomes. In patients with metastatic melanoma, the level of Faecalibacterium prausnitzi at baseline was predictive of response to anti-PD-1 (programmed death-1) or anti-CTLA-4 therapy. EXL01 is a pharmacological preparation of Faecalibacterium prausnitzii strains. Preclinical murine study suggests that the administration of EXL01 could reverse the resistance to ICI induced by antibiotics (unpublished data).
We thus plan to test the concept of microbiota modification in patients treated with standard-of-care approved first-line immunotherapy for advanced HCC. We would include patients refractory to first-line treatment, and test the addition of EXL01 to standard-of-care approved first-line immunotherapy in order to reverse resistance.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- EXL01
- Keywords
- Immunotherapy, microbiome, resistance, dysbiosis, Faecalibacterium prausnitzii
- Medical subject headings
- Carcinoma, Hepatocellular, Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EXL01Drug
EXL01 contains an unmodified single strain of F. prausnitzii
| Study group | Role | What they receive |
|---|---|---|
| standard-of-care approved first-line immunotherapy- EXL01 | Experimental | Patients treated with atezolizumab-bevacizumab ou durvalumab with the addition of the experimental treatment exl01, 1 capsule per day for a maximum of 12 months. Receives: Drug: EXL01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate at week12
ORR defined as the best observed overall tumor response (BOR) from inclusion to W12, according RECIST 1.1 criteria
Measured: At week12
Adverse event
safety of atezolizumab-bevacizumab with bacterial supplementation EXL01
Measured: Maximum 15 month after le first EXL01 administration
Secondary outcomes (6)
Overall tumor response
Overall tumor response according to the mRECIST, RECIST 1.1 and iRECIST.
Measured: At week6; at week12; at month 6, at month12
Objective Response Rate at week12
ORR at week 12 according to mRECIST and iRECIST criteria
Measured: at week 12
Objective Response Rate at M6 and M12
The ORR at M6, M12, according to the mRECIST, RECIST 1.1 and iRECIST criteria.
Measured: At month 6, at month 12
The Disease control rate (DCR),
The Disease control rate (DCR), as the proportion of patients with BOR as CR, PR or stable disease (SD) defined according to the mRECIST, RECIST 1.1 and iRECIST criteria at W12, M6, M12.
Measured: At week12; at month 6, at month12
The Progression-Free Survival
The Progression-Free Survival, defined as the time from patient inclusion to progression or death from any cause.
Measured: Maximum 12 month after the fisrt EXL01 administration
Overall survival (OS)
The Overall Survival, defined as the time from patient inclusion to death from any cause
Measured: Maximum 15 month after the fisrt EXL01 administration of the last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2024
- Study start12 Mar 2025
- Primary completion12 Mar 2026 (estimated)
- Study completion12 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Center Eugene Marquis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Héloise BOURIEN, Dr, Principal investigator, Centre de lutte contre le cancer Eugène Marquis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06551272
- Sponsor's protocol ID
- 2023-1-69-001
- Acronym
- MOTHER
- Status last verified
- Jul 2025
- First submitted
- 9 Aug 2024
- Last updated
- 5 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT06551272
- Acronym / sponsor ID
- MOTHER / 2023-1-69-001
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Immunotherapy, microbiome, resistance, dysbiosis, Faecalibacterium prausnitzii
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Center Eugene MarquisUniversity, hospital or other
- Study start
- 12 Mar 2025 (actual)
- Primary completion
- 12 Mar 2026 (estimated)
- Study completion
- 12 Dec 2026 (estimated)
- First posted
- 13 Aug 2024 (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.
Hepatocellular carcinoma (HCC) is the most common liver primary cancer with a high rate of mortality. Since the results of IMbrave150, immunotherapy have emerged as a standard of care for HCC patients advanced and/or unresectable in first line of treatment. The objective response rate was about 30%, but half of patients would present only stable disease and about 20% progressive disease.
Faecalibacterium prausnitzii is one of the most abundant bacterial in human gut microbiota, around 5% of total bacteria in feces.
For patients with metastatic melanoma, treated with ipilimumab, an antibody targeting CTLA-4 (Cytotoxic T-lymphocyte-associated antigen 4), patients with a baseline gut microbiota enriched with Faecalibacterium had a significantly better clinical outcomes. In patients with metastatic melanoma, the level of Faecalibacterium prausnitzi at baseline was predictive of response to anti-PD-1 (programmed death-1) or anti-CTLA-4 therapy. EXL01 is a pharmacological preparation of Faecalibacterium prausnitzii strains. Preclinical murine study suggests that the administration of EXL01 could reverse the resistance to ICI induced by antibiotics (unpublished data).
We thus plan to test the concept of microbiota modification in patients treated with standard-of-care approved first-line immunotherapy for advanced HCC. We would include patients refractory to first-line treatment, and test the addition of EXL01 to standard-of-care approved first-line immunotherapy in order to reverse resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| standard-of-care approved first-line immunotherapy- EXL01 | Experimental | Drug: EXL01Patients treated with atezolizumab-bevacizumab ou durvalumab with the addition of the experimental treatment exl01, 1 capsule per day for a maximum of 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male and Female
- Age ≥18 years at time of signing informed consent
- Presenting with HCC, diagnosed either by histological or radiological criteria as described by EASL
- Locally advanced or metastatic and/or unresectable HCC according a Multidisciplinary Team meeting
- Progressive disease after exposure to standard-of-care approved first-line immunotherapy
Key exclusion criteria (31 listed)
- Partial response achieved under standard-of-care approved first-line immunotherapy
- CTCAE Grade ≥3 or more toxicity under standard-of-care approved first-line immunotherapy, or persistent toxicity Grade >1
- Liver involvement > 50%
- Presence of major macro vascular invasion (except Vp1/Vp2)
- Pregnant woman, or breastfeeding or women of child-bearing potential with no adequate contraception (see §4.3.1)
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 |
|---|---|---|
| EXL01EXL01 contains an unmodified single strain of F. prausnitzii | Drug | standard-of-care approved first-line immunotherapy- EXL01 |
Primary outcome
Objective Response Rate at week12
Time frame: At week12
ORR defined as the best observed overall tumor response (BOR) from inclusion to W12, according RECIST 1.1 criteria
Adverse event
Time frame: Maximum 15 month after le first EXL01 administration
safety of atezolizumab-bevacizumab with bacterial supplementation EXL01
6 secondary outcomes
Overall tumor response
Time frame: At week6; at week12; at month 6, at month12
Objective Response Rate at week12
Time frame: at week 12
Objective Response Rate at M6 and M12
Time frame: At month 6, at month 12
The Disease control rate (DCR),
Time frame: At week12; at month 6, at month12
The Progression-Free Survival
Time frame: Maximum 12 month after the fisrt EXL01 administration
Overall survival (OS)
Time frame: Maximum 15 month after the fisrt EXL01 administration of the last patient
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2025.
- Individual participant dataSharing planned: No
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
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.
Marion TROCHET contact
Héloise BOURIEN, Dr principal investigator
Centre de lutte contre le cancer Eugène Marquis
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EXL01 in people with Hepatocellular Carcinoma, run by Center Eugene Marquis at 6 sites in France.
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 11 inclusion and 31 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: looking for participants now, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Valérie JOLAINE (0299253036 ext. +33, v.jolaine@rennes.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate at week12 (time frame: At week12). The study lists 2 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 5 Aug 2025.