MICROBIOTA MODIFICATION FOR IMMUNO-ONCOLOGY IN HEPATOCELLULAR CARCINOMA - “MOTHER”
- Conditions
- Hepatocellular carcinoma
- Registration Number
- 2023-508201-25-00
- Lead Sponsor
- Centre De Lutte Contre Le Cancer Eugene Marquis
- Brief Summary
To evaluate efficacy of atezolizumab-bevacizumab with bacterial supplementation in HCC patients progressive to first line immunotherapy
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 34
Male or female
Signed written Informed consent
Aged ≥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-based
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
Partial response achieved under first-line immunotherapy-based combination
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
CTCAE Grade ≥3 or more toxicity under first-line immunotherapy-based combination 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
Under curatorship, guardianship, safeguard of justice or deprived of liberty
History of serious autoimmune disease
Specific contra-indication to atezolizumab-bevacizumab: 1) Thromboembolic events in the 3 months prior to inclusion 2) Prior bleeding event due to untreated or incompletely treated esophageal and / or gastric varices within 6 months’ prior inclusion 3) Has a history of hypersensitivity to the atezolizumab or to any of the excipients listed in section 6.1 of the SmPC of atezolizumab and bevacizumab or to any of the excipients listed in section 6.1 of the SmPC 4) Uncontrolled hypertension 5) Clinically significant cardiovascular disease such as pre-existing coronary artery disease, or congestive heart failure 6) Proteinuria
specific contra-indication 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
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
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.
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The Objective Response Rate at W12, defined as the proportion of patients with a Complete objective tumor Response (CR) or a Partial objective tumor Response (PR) from inclusion to week 12. The objective tumor response is defined as the best overall tumor response (BOR) observed in a patient within all-time points between inclusion to the W12 visit, according to the RECIST 1.1. The Objective Response Rate at W12, defined as the proportion of patients with a Complete objective tumor Response (CR) or a Partial objective tumor Response (PR) from inclusion to week 12. The objective tumor response is defined as the best overall tumor response (BOR) observed in a patient within all-time points between inclusion to the W12 visit, according to the RECIST 1.1.
The overall tumor response observed at first imaging after 2 cycles of standard of care immunotherapy (W6 for patients treated with atezolizumab-bevacizumab cohort or W8 for patients treated with durvalumab- tremelimumab cohort), W12, M6, M12 according to the mRECIST, RECIST 1.1 and iRECIST criteria. The overall tumor response observed at first imaging after 2 cycles of standard of care immunotherapy (W6 for patients treated with atezolizumab-bevacizumab cohort or W8 for patients treated with durvalumab- tremelimumab cohort), W12, M6, M12 according to the mRECIST, RECIST 1.1 and iRECIST criteria.
The ORR at W12, according to the mRECIST, and iRECIST criteria. The ORR at W12, according to the mRECIST, and iRECIST criteria.
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. 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.
The Progression-Free Survival, defined as the time from patient inclusion to progression or death from any cause. The Progression-Free Survival, defined as the time from patient inclusion to progression or death from any cause.
The Overall Survival, defined as the time from patient inclusion to death from any cause. The Overall Survival, defined as the time from patient inclusion to death from any cause.
The ORR at M6, M12, according to the mRECIST, RECIST 1.1 and iRECIST criteria. The ORR at M6, M12, according to the mRECIST, RECIST 1.1 and iRECIST criteria.
- Secondary Outcome Measures
Name Time Method Frequency of adverse events, graded according to the last up-to-date NCI-CTCAE classification. Adverse events are monitored from inclusion to 30 days after the last EXL01 intake. Frequency of adverse events, graded according to the last up-to-date NCI-CTCAE classification. Adverse events are monitored from inclusion to 30 days after the last EXL01 intake.
Trial Locations
- Locations (6)
Hopital Beaujon
🇫🇷Clichy, France
Hospital Hotel Dieu
🇫🇷Nantes, France
Centre Hospitalier Universitaire De Bordeaux
🇫🇷Pessac, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre De Lutte Contre Le Cancer Eugene Marquis
🇫🇷Rennes Cedex, France
Hopital Avicenne
🇫🇷Bobigny Cedex, France
Hopital Beaujon🇫🇷Clichy, FranceMohamed BOUATTOURSite contact0140875614mohamed.bouattour@aphp.fr