Evaluation de l’intérêt de combiner un vaccin inducteur de CD4-Th1 dérivé de la télomérase avec un traitement par atezolizumab et bevacizumab chez des patients avec un carcinome hépatocellulaire non résécable : une étude de phase II randomisée preuve du concept
- Conditions
- Patients with locally advanced, metastatic or unresectable hepatocellular carcinomaMedDRA version: 21.0Level: LLTClassification code: 10019828Term: Hepatocellular carcinoma non-resectable Class: 10029104Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- CTIS2022-500643-20-00
- Lead Sponsor
- CHUR Of Besançon
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 104
Signed informed consent, Age = 18 years, Measurable disease defined according to RECIST v1.1 guidelines, Patients who have received previous chemoembolization, radioembolization and/or radiotherapy should have recovered from any treatment related toxicity, to a level of = grade 1 (according to National Cancer Institute [NCI] common terminology criteria for adverse events, version 5 (CTCAE v5) with the exception of Grade 2 alopecia, Performance status < 2, Child–Pugh Class A status, 1. Signed informed consent 2. Histologically confirmed hepatocellular carcinoma 3. Locally advanced, metastatic, or unresectable disease 4. Patient who had not previously received systemic anti-cancer treatment 5. Age = 18 years 6. Measurable disease defined according to RECIST v1.1 guidelines (Appendix 1; Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.) 7. Patients who have received previous chemoembolization, radioembolization and/or radiotherapy should have recovered from any treatment related toxicity, to a level of = grade 1 (according to National Cancer Institute [NCI] common terminology criteria for adverse events, version 5 (CTCAE v5; Appendix 2) with the exception of Grade 2 alopecia 8. Performance status < 2 (Appendix 3) 9. Child–Pugh Class A status (Appendix 4) 10. Females must be using highly effective contraceptive measures (see Section V-5-1), and have a negative pregnancy test prior to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening: •Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. •Women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution. •Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 5 months following discontinuation of study drug. Patients should refrain from donating sperm from the start of dosing until 5 months after discontinuing study treatment. 11. Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests: - For patients with active HBV: HBV DNA <500 IU/ml during screening, initiation of anti-HBV treatment at least 14 days prior to randomization and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., entecavir) - Patients with HCV, either with resolved infection (as evidenced by detectable antibody) or chronic infection (as evidence by detectable HCV RNA), are eligible 12. Performance of an esophagogastroduodenoscopy and assessment and treatment of varices of all sizes per local standard of care prior to randomization 13. Patient affiliated to or beneficiary of French social security system 14. Ability to comply with the study protocol, in the Investigator’s judgment., Females must be using highly effective contraceptive measures and have a negative pregnancy test prior
Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy, History of encephalopathy, Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization, Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition, HIV positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus, Any immunosuppressive therapy (i.e. corticosteroids >10mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy, Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs)., Prior allogeneic bone marrow transplantation or prior solid organ transplantation, History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of atezolizumab or bevacizumab formulation, History of idiopathic or secondary pulmonary fibrosis (History of radiation pneumonitis in the radiation field fibrosis is permitted), or evidence of active pneumonitis requiring a systemic treatment with 28 days before the planned start of study therapy, Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer, Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study, Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study, Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (prednisone or prednisolone = 10 mg/day is allowed) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to the start of the study treatment, Patient with intra-alveolar hemorrhage, pulmonary fibrosis, or uncontrolled asthma, or chronic obstructive disease (COPD), defined as at least one hospitalization within 4 months prior to enrollment or as at least 3 exacerbations during the last year prior to enrollment, Patients requiring oxygen therapy, Patients with LEVF<40%, Hospitalization for cardiovascular or pulmonary disease within 4 weeks prior to enrollment, Receipt of a live, attenuated vaccine within 4 weeks prior to inclusion or anticipation that such a live, attenuated vaccine will be required during the study Note: Patients must agree not to receive live, attenuated influenza vaccine (e.g.,FluMist®) within 28 days prior to randomization, during treatment or within 5 months following the last dose of atezolizumab, Current or recent (within 10 days prior of Day 1 of Cycle 1) use of aspirine (>325 mg/day) or current or recent treatment with dipyramidole, ticlopidine,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method