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TERTIO : 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
EU CTIS ID: 2022-500643-20-00
What this study is testing
to assess the efficacy of a strategy combining UCPVax and atezolizumab plus bevacizumab combination in patients with unresectable hepatocellular carcinoma by evaluation, according to RECIST v1.1, of the objective response rate at 6 months.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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
You likely can't join if
- 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
See the full eligibility criteria
Who can join
- 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 to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential
- 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
- Performance of an esophagogastroduodenoscopy and assessment and treatment of varices of all sizes per local standard of care prior to randomization
- Patient affiliated to or beneficiary of French social security system
- Ability to comply with the study protocol, in the Investigator’s judgment
- Histologically confirmed hepatocellular carcinoma
- Locally advanced, metastatic, or unresectable disease
- Patient who had not previously received systemic anti-cancer treatment
What rules you out
- 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, clopidogrel, and cilostazol.
- Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
- Current or recent (within 10 days prior to Day 1 of Cycle 1) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose - Prophylactic anticoagulation for the patency of venous access devices is allowed provided the activity of the agent results in an INR <1.5 x ULN and aPTT is within normal limits (according to institutional standards) within 14 days prior to Day 1 of Cycle 1. - Prophylactic use of low-molecular-weight heparin (LMWH) (i.e., enoxaparin 40 mg/day) is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) is not recommended due to bleeding risk.
- Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID).
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to Day 1 of Cycle 1.
- Major surgical procedure within 4 weeks prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the study.
- Inadequate hematology function: Lymphocyte count at baseline <800/mm3; neutrophil count <1000/mm3, platelets <75000/mm3 (without transfusion), Hemoglobin <9g/dL (patients may be transfused to meet this criterion).
- Inadequate hepatic function: bilirubin 3 fold ULN, AST/ALT 5 fold ULN, International normalized thromboplastin time ratio >2
- Inadequate renal function: MDRD CrCl <30ml/min, Urine dipstick for proteinuria ≥2+ (within 7 days prior to Day 1 of Cycle1) - Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1g of protein in 24 hours.
- Others inadequate laboratory values: serum albumin<28 g/L; troponin > ULN; BNP > ULN.
- Active alcohol or drug abuse
- Current participation in a study of an investigational agent or in the period of exclusion
- Patient under guardianship, curatorship or under the protection of justice
- Know fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula
- Uncontrolled tumor-related pain: exposing patients to risk of exposure to corticoids or iterative hospitalizations. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to inclusion. Patients should be recovered from the effects of radiation. There is no required minimum recovery period
- Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.