Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure
NCT ID: NCT06045975
Last Updated: 2025-04-02
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
RECRUITING
Clinical Phase
PHASE2
Total Enrollment
30 participants
Study Classification
INTERVENTIONAL
Study Start Date
2024-03-28
Study Completion Date
2028-09-28
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
This project is a Phase 2 trial testing the safety and efficacy of treatment with Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting in patients with BCLC A HCC treated by by percutaneous ablation (PA) procedure in a curative intent.
DUMELEP is a Multicentre, Phase 2 trial
Eligible patients will receive consecutively:
1. 1 Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting
2. percutaneous ablation procedure in a curative attempt at Day 30
3. 11 monthly Durvalumab 1500 mg infusions.
4. Classical follow-up during an additional year (every 3 months)
DUMELEP is a Multicentre, Phase 2 trial
Eligible patients will receive consecutively:
1. 1 Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting
2. percutaneous ablation procedure in a curative attempt at Day 30
3. 11 monthly Durvalumab 1500 mg infusions.
4. Classical follow-up during an additional year (every 3 months)
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
NCT03298451
Hepatocellular Carcinoma
ACTIVE_NOT_RECRUITING
PHASE3
A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma
NCT02519348
Hepatocellular Carcinoma
ACTIVE_NOT_RECRUITING
PHASE2
Durvalumab and Tremelimumab in Resectable HCC
NCT05440864
Hepatocellular Carcinoma
RECRUITING
PHASE2
Durvalumab and Tremelimumab With or Without Hepatic Arterial Infusion of Chemotherapy in Hepatocellular Carcinoma
NCT06904170
Hepatocellular Carcinoma
NOT_YET_RECRUITING
PHASE2/PHASE3
Safety and Efficacy of Tremelimumab+Durvalumab(MEDI4736)+TACE in Unresectable Hepatocellular Carcinoma
NCT06911255
Hepatocellular Carcinoma (HCC)
Unresectable Hepatocellular Carcinoma
RECRUITING
PHASE1/PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Immunotherapy is currently the gold standard for first-line treatment of advanced HCC based of the combination of check-point inhibitors (CPI). The first approved regimen is based on the association of atezolizumab and bevacizumab, an antiangiogenic molecule. More recently, the HIMALAYA trial demonstrated the superiority of durvalumab-tremelimumab over sorafenib, establishing a new first-line option.The combination of Immunotherapy and locoregional treatments in earlier HCC stages may reduce relapse rates. Preliminary data from the IMBRAVE 050 trail reports lower rates of recurrence following HCC percutaneous ablation (PA) or resection associated with atezolizumab and bevacizumab in adjuvant setting.PA procedures and most likely electroporation induce T-cell recruitment that may foster immunomodulation. In particular, radiofrequency ablation (RFA) can lead to stimulation of NK cells with a more differentiated and proactivatory phenotypic profile with general increase of functional activities. As compared with RFA, these local changes of IRE induce more robust systemic effects, including both tumorigenic and immunogenic events. Indeed, the preservation of the tumor microvasculature and extracellular matrix within the coagulated zone would favour infiltration by anti tumoral immune cells. These observations are relevant for development of neoadjuvant and adjuvant immunotherapeutic strategies in the setting of HCC treated by percutaneous ablation, and particularly IRE .
Neoadjuvant and adjuvant trials using these new molecules must now be cautiously designed based on the rigorous selection of special populations and therapeutic indications based on the following criteria:
* Exclusion of early forms of HCC with low probability of recurrence for statistical power issues
* Inclusion of patients with HCC treated in "curative intent" by new PA techniques such as electroporation
* Selective inclusion of patients treated with PA whose immunomodulatory properties are recognized
Neoadjuvant and adjuvant trials using these new molecules must now be cautiously designed based on the rigorous selection of special populations and therapeutic indications based on the following criteria:
* Exclusion of early forms of HCC with low probability of recurrence for statistical power issues
* Inclusion of patients with HCC treated in "curative intent" by new PA techniques such as electroporation
* Selective inclusion of patients treated with PA whose immunomodulatory properties are recognized
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
HCC - Hepatocellular Carcinoma
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
NA
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Durvalumab/Tremelimumab
Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
Group Type
EXPERIMENTAL
Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
Intervention Type
DRUG
* Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting followed by PA procedure at Day 30+/-7 days
* 11 monthly Durvalumab 1500 mg infusions.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
* Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting followed by PA procedure at Day 30+/-7 days
* 11 monthly Durvalumab 1500 mg infusions.
Intervention Type
DRUG
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Male or female patients ≥ 18 years of age
* Histological or radiological diagnosis of HCC
* Patients with newly diagnosed or recurrent HCC (following a previous curative procedure performed at least 6 months before inclusion) eligible for PA as assessed by multidisciplinary board corresponding to BCLC A stage:
* Uninodular HCC ≥ 2 cm and ≤ 5 cm, no macroscopic vascular invasion
* Multinodular maximum 3 nodules ≤ 3 cm
* Body weight \>30 kg
* Liver function status Child-Pugh Class A
* \<\<Eastern Cooperative Oncology Group (ECOG)\>\>\<\<World Health Organisation (WHO) performance status of 0 or 1
* Adequate bone marrow, liver and renal function as assessed by the following laboratory tests:
* Total bilirubin ≤ 2 mg/dL
* Serum creatinine ≤ 1.5 x ULN
* Lipase ≤ 2 x ULN
* Prothrombine time-international normalized ratio (PT-INR) \< 2.3 and PTT \< 1.5
* Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2
* Life expectancy ≥ 3 months
* Women of childbearing potential (WOCBP) need to accept one effective method of contraception until 3 months after the last infusion of durvalumab and avoid pregnancy
* Patients affiliated to a Social Security System
* Written informed consent signed (patients must be free from tutelle, curatelle or sauvegarde de justice)
* Haemoglobin ≥9.0 g/dL
* Absolute neutrophil count (ANC ≥1.0 × 109/L)
* Platelet count ≥75 × 109/L
* Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.)
* AST (SGOT) and ALT (SGPT) ≤5x ULN
* Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
* Patients must have a life expectancy of at least 12 weeks
* At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at pre inclusion/inclusion. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to inclusion
* Patients infected with HCV must be managed according to international recommendations
* Antiviral therapy in case of HBV active infection or inactive carriage
* Patients with contraindications to PA procedure (Pacemakers or patients who have a history of cardiac arrhythmias or irregular heartbeats in case of IRE, ascites, Coagulopathy, Ongoing infection)
* Patients with contraindication to contrast medium intravenous injection either gadolinium or iodinate
* Prior liver transplantation
* Uncontrolled HCC defined by the absence of remission \> 6months following resection of percutaneous ablation at time of inclusion
* Prior systemic treatment for HCC, in particular agents targeting T-cell costimulation or checkpoint pathways (including those targeting PD-1, PD-L1 or PD-L2, CD137, or cytotoxic Tlymphocyte antigen \[CTLA-4\]).
* Patients with uncontrolled HBV infection and viral load above 100 IU/mL.
* Patients with large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention
* Past or concurrent history of neoplasm other than HCC, except for in situ carcinoma of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumors. Any cancer curatively treated \> 3 years prior to study entry is permitted
* Major surgical procedure or significant traumatic injury within 28 days before enrolment
* Congestive heart failure New York Heart Association (NYHA) ≥ class 2
* Unstable angina or myocardial infarction within the past 6 months before enrolment
* Grade 3 (severe) hypertension ≥180 and/or ≥110 mmHG (systolic and diastolic, according to National Heart Foundation 2016)
* Patients with phaeochromocytoma
* Refractory ascites according to EASL guidelines definition (ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment)
* Persistent proteinuria of NCI-CTCAE version 5.0 ≥ Grade 3
* Ongoing infection \> Grade 2 according to NCI-CTCAE version 5.0.
* Patients with chronic hepatitis B or inactive carriers for HBV must be under anti-HBV treatment
* Clinically significant bleeding NCI-CTCAE version 5.0 ≥ Grade 3 within 30 days before enrolment
* Any psychological, familial, sociological, geographical or illness or medical condition that could jeopardize the safety of the patient and/or his compliance with the study protocol and follow-up procedure
* Known history of human immunodeficiency virus (HIV) infection
* Non-healing wound, ulcer or bone fracture
* Known hypersensitivity to the study drug or excipients in the formulation
* Any malabsorption condition
* Breast feeding
* Pregnancy
* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab and tremelimumab combination therapy.
* Participation in another clinical study with an investigational product during the last 6 months
* Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
* Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. \<\<amend as required based on any combination studies with other anticancer agents\>\>
* Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
* History of allogenic organ transplantation.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician
5. Patients with celiac disease controlled by diet alone
* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
* History of another primary malignancy except for :
1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
3. Adequately treated carcinoma in situ without evidence of disease
* History of leptomeningeal carcinomatosis
* Study excludes patients with -brain metastases or spinal cord compression: Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Brain metastases will not be recorded as RECIST Target Lesions at baseline if study allows patients with brain metastases.
* Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (RECIST)) for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases.
These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10mg/day of prednisone or its equivalent \<\<and anti-convulsants\>\> for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
* Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
* History of active primary immunodeficiency
* Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab and tremelimumab combination therapy.
* Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
* Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
* Patients who have received prior anti-PD-1, anti-PD-L1 or anti-CTLA-4:
1. Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
2. All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
3. Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
4. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
* Histological or radiological diagnosis of HCC
* Patients with newly diagnosed or recurrent HCC (following a previous curative procedure performed at least 6 months before inclusion) eligible for PA as assessed by multidisciplinary board corresponding to BCLC A stage:
* Uninodular HCC ≥ 2 cm and ≤ 5 cm, no macroscopic vascular invasion
* Multinodular maximum 3 nodules ≤ 3 cm
* Body weight \>30 kg
* Liver function status Child-Pugh Class A
* \<\<Eastern Cooperative Oncology Group (ECOG)\>\>\<\<World Health Organisation (WHO) performance status of 0 or 1
* Adequate bone marrow, liver and renal function as assessed by the following laboratory tests:
* Total bilirubin ≤ 2 mg/dL
* Serum creatinine ≤ 1.5 x ULN
* Lipase ≤ 2 x ULN
* Prothrombine time-international normalized ratio (PT-INR) \< 2.3 and PTT \< 1.5
* Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2
* Life expectancy ≥ 3 months
* Women of childbearing potential (WOCBP) need to accept one effective method of contraception until 3 months after the last infusion of durvalumab and avoid pregnancy
* Patients affiliated to a Social Security System
* Written informed consent signed (patients must be free from tutelle, curatelle or sauvegarde de justice)
* Haemoglobin ≥9.0 g/dL
* Absolute neutrophil count (ANC ≥1.0 × 109/L)
* Platelet count ≥75 × 109/L
* Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.)
* AST (SGOT) and ALT (SGPT) ≤5x ULN
* Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
* Patients must have a life expectancy of at least 12 weeks
* At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at pre inclusion/inclusion. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to inclusion
* Patients infected with HCV must be managed according to international recommendations
* Antiviral therapy in case of HBV active infection or inactive carriage
* Patients with contraindications to PA procedure (Pacemakers or patients who have a history of cardiac arrhythmias or irregular heartbeats in case of IRE, ascites, Coagulopathy, Ongoing infection)
* Patients with contraindication to contrast medium intravenous injection either gadolinium or iodinate
* Prior liver transplantation
* Uncontrolled HCC defined by the absence of remission \> 6months following resection of percutaneous ablation at time of inclusion
* Prior systemic treatment for HCC, in particular agents targeting T-cell costimulation or checkpoint pathways (including those targeting PD-1, PD-L1 or PD-L2, CD137, or cytotoxic Tlymphocyte antigen \[CTLA-4\]).
* Patients with uncontrolled HBV infection and viral load above 100 IU/mL.
* Patients with large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention
* Past or concurrent history of neoplasm other than HCC, except for in situ carcinoma of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumors. Any cancer curatively treated \> 3 years prior to study entry is permitted
* Major surgical procedure or significant traumatic injury within 28 days before enrolment
* Congestive heart failure New York Heart Association (NYHA) ≥ class 2
* Unstable angina or myocardial infarction within the past 6 months before enrolment
* Grade 3 (severe) hypertension ≥180 and/or ≥110 mmHG (systolic and diastolic, according to National Heart Foundation 2016)
* Patients with phaeochromocytoma
* Refractory ascites according to EASL guidelines definition (ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment)
* Persistent proteinuria of NCI-CTCAE version 5.0 ≥ Grade 3
* Ongoing infection \> Grade 2 according to NCI-CTCAE version 5.0.
* Patients with chronic hepatitis B or inactive carriers for HBV must be under anti-HBV treatment
* Clinically significant bleeding NCI-CTCAE version 5.0 ≥ Grade 3 within 30 days before enrolment
* Any psychological, familial, sociological, geographical or illness or medical condition that could jeopardize the safety of the patient and/or his compliance with the study protocol and follow-up procedure
* Known history of human immunodeficiency virus (HIV) infection
* Non-healing wound, ulcer or bone fracture
* Known hypersensitivity to the study drug or excipients in the formulation
* Any malabsorption condition
* Breast feeding
* Pregnancy
* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab and tremelimumab combination therapy.
* Participation in another clinical study with an investigational product during the last 6 months
* Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
* Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. \<\<amend as required based on any combination studies with other anticancer agents\>\>
* Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
* History of allogenic organ transplantation.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician
5. Patients with celiac disease controlled by diet alone
* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
* History of another primary malignancy except for :
1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
3. Adequately treated carcinoma in situ without evidence of disease
* History of leptomeningeal carcinomatosis
* Study excludes patients with -brain metastases or spinal cord compression: Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Brain metastases will not be recorded as RECIST Target Lesions at baseline if study allows patients with brain metastases.
* Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (RECIST)) for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases.
These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10mg/day of prednisone or its equivalent \<\<and anti-convulsants\>\> for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
* Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
* History of active primary immunodeficiency
* Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab and tremelimumab combination therapy.
* Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
* Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
* Patients who have received prior anti-PD-1, anti-PD-L1 or anti-CTLA-4:
1. Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
2. All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
3. Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
4. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
Minimum Eligible Age
18 Years
Maximum Eligible Age
85 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
AstraZeneca
INDUSTRY
Sponsor Role
collaborator
Assistance Publique - Hôpitaux de Paris
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Perre NAHON, MD-PhD
Role: PRINCIPAL_INVESTIGATOR
APHP
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Hospitl Avicenne
Bobigny, , France
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
France
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Trinchet JC, Bourcier V, Chaffaut C, Ait Ahmed M, Allam S, Marcellin P, Guyader D, Pol S, Larrey D, De Ledinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Goria O, Cales P, Peron JM, Alric L, Bourliere M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grange JD, Buffet C, Bacq Y, Wartelle C, Dao T, Benhamou Y, Pilette C, Silvain C, Christidis C, Capron D, Thiefin G, Hillaire S, Di Martino V, Nahon P, Chevret S; ANRS CO12 CirVir Group. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort). Hepatology. 2015 Sep;62(3):737-50. doi: 10.1002/hep.27743. Epub 2015 Mar 20.
Reference Type
BACKGROUND
N'Kontchou G, Mahamoudi A, Aout M, Ganne-Carrie N, Grando V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M, Seror O. Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology. 2009 Nov;50(5):1475-83. doi: 10.1002/hep.23181.
Reference Type
BACKGROUND
Nault JC, Sutter O, Nahon P, Ganne-Carrie N, Seror O. Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations. J Hepatol. 2018 Apr;68(4):783-797. doi: 10.1016/j.jhep.2017.10.004. Epub 2017 Oct 13.
Reference Type
BACKGROUND
Seror O. Ablative therapies: Advantages and disadvantages of radiofrequency, cryotherapy, microwave and electroporation methods, or how to choose the right method for an individual patient? Diagn Interv Imaging. 2015 Jun;96(6):617-24. doi: 10.1016/j.diii.2015.04.007. Epub 2015 May 14.
Reference Type
BACKGROUND
Seror O, N'Kontchou G, Ibraheem M, Ajavon Y, Barrucand C, Ganne N, Coderc E, Trinchet JC, Beaugrand M, Sellier N. Large (>or=5.0-cm) HCCs: multipolar RF ablation with three internally cooled bipolar electrodes--initial experience in 26 patients. Radiology. 2008 Jul;248(1):288-96. doi: 10.1148/radiol.2481071101. Epub 2008 May 15.
Reference Type
BACKGROUND
Sutter O, Calvo J, N'Kontchou G, Nault JC, Ourabia R, Nahon P, Ganne-Carrie N, Bourcier V, Zentar N, Bouhafs F, Sellier N, Diallo A, Seror O. Safety and Efficacy of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma Not Amenable to Thermal Ablation Techniques: A Retrospective Single-Center Case Series. Radiology. 2017 Sep;284(3):877-886. doi: 10.1148/radiol.2017161413. Epub 2017 Apr 28.
Reference Type
BACKGROUND
Cheng RG, Bhattacharya R, Yeh MM, Padia SA. Irreversible Electroporation Can Effectively Ablate Hepatocellular Carcinoma to Complete Pathologic Necrosis. J Vasc Interv Radiol. 2015 Aug;26(8):1184-8. doi: 10.1016/j.jvir.2015.05.014. Epub 2015 Jun 26.
Reference Type
BACKGROUND
Niessen C, Beyer LP, Haimerl M, Schicho A, Stroszczynski C, Wiggermann P, Jung EM. Percutaneous irreversible electroporation of hepatocellular carcinoma: Contrast-enhanced ultrasound-findings during 1-year follow-up. Clin Hemorheol Microcirc. 2019;72(1):85-93. doi: 10.3233/CH-180449.
Reference Type
BACKGROUND
Niessen C, Beyer LP, Pregler B, Dollinger M, Trabold B, Schlitt HJ, Jung EM, Stroszczynski C, Wiggermann P. Percutaneous Ablation of Hepatic Tumors Using Irreversible Electroporation: A Prospective Safety and Midterm Efficacy Study in 34 Patients. J Vasc Interv Radiol. 2016 Apr;27(4):480-6. doi: 10.1016/j.jvir.2015.12.025. Epub 2016 Feb 26.
Reference Type
BACKGROUND
Niessen C, Thumann S, Beyer L, Pregler B, Kramer J, Lang S, Teufel A, Jung EM, Stroszczynski C, Wiggermann P. Percutaneous Irreversible Electroporation: Long-term survival analysis of 71 patients with inoperable malignant hepatic tumors. Sci Rep. 2017 Mar 7;7:43687. doi: 10.1038/srep43687.
Reference Type
BACKGROUND
Bhutiani N, Philips P, Scoggins CR, McMasters KM, Potts MH, Martin RC. Evaluation of tolerability and efficacy of irreversible electroporation (IRE) in treatment of Child-Pugh B (7/8) hepatocellular carcinoma (HCC). HPB (Oxford). 2016 Jul;18(7):593-9. doi: 10.1016/j.hpb.2016.03.609. Epub 2016 May 1.
Reference Type
BACKGROUND
Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8.
Reference Type
BACKGROUND
El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
Reference Type
BACKGROUND
Behm B, Di Fazio P, Michl P, Neureiter D, Kemmerling R, Hahn EG, Strobel D, Gress T, Schuppan D, Wissniowski TT. Additive antitumour response to the rabbit VX2 hepatoma by combined radio frequency ablation and toll like receptor 9 stimulation. Gut. 2016 Jan;65(1):134-43. doi: 10.1136/gutjnl-2014-308286. Epub 2014 Dec 18.
Reference Type
BACKGROUND
Zerbini A, Pilli M, Laccabue D, Pelosi G, Molinari A, Negri E, Cerioni S, Fagnoni F, Soliani P, Ferrari C, Missale G. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology. 2010 May;138(5):1931-42. doi: 10.1053/j.gastro.2009.12.051. Epub 2010 Jan 11.
Reference Type
BACKGROUND
Bulvik BE, Rozenblum N, Gourevich S, Ahmed M, Andriyanov AV, Galun E, Goldberg SN. Irreversible Electroporation versus Radiofrequency Ablation: A Comparison of Local and Systemic Effects in a Small-Animal Model. Radiology. 2016 Aug;280(2):413-24. doi: 10.1148/radiol.2015151166. Epub 2016 Jan 27.
Reference Type
BACKGROUND
Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.
Reference Type
BACKGROUND
Iida N, Nakamoto Y, Baba T, Nakagawa H, Mizukoshi E, Naito M, Mukaida N, Kaneko S. Antitumor effect after radiofrequency ablation of murine hepatoma is augmented by an active variant of CC Chemokine ligand 3/macrophage inflammatory protein-1alpha. Cancer Res. 2010 Aug 15;70(16):6556-65. doi: 10.1158/0008-5472.CAN-10-0096. Epub 2010 Jul 27.
Reference Type
BACKGROUND
Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, Qin S, Tai DW, Lim HY, Yau T, Yong WP, Cheng AL, Gasbarrini A, Damian S, Bruix J, Borad M, Bendell J, Kim TY, Standifer N, He P, Makowsky M, Negro A, Kudo M, Abou-Alfa GK. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. J Clin Oncol. 2021 Sep 20;39(27):2991-3001. doi: 10.1200/JCO.20.03555. Epub 2021 Jul 22.
Reference Type
BACKGROUND
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.
Reference Type
BACKGROUND
Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, Sukeepaisarnjaroen W, Kang YK, Van Dao T, De Toni EN, Rimassa L, Breder V, Vasilyev A, Heurgue A, Tam VC, Mody K, Thungappa SC, Ostapenko Y, Yau T, Azevedo S, Varela M, Cheng AL, Qin S, Galle PR, Ali S, Marcovitz M, Makowsky M, He P, Kurland JF, Negro A, Sangro B. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022 Aug;1(8):EVIDoa2100070. doi: 10.1056/EVIDoa2100070. Epub 2022 Jun 6.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
APHP220729
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Durvalumab and Tremelimumab After Radioembolization for the Treatment of Unresectable, Locally Advanced Liver Cancer
NCT04605731
ACTIVE_NOT_RECRUITING
PHASE1
Durvalumab With/Without Tremelimumab After Palliative Hypofractionated Radiotherapy for Hepatocellular Carcinoma
NCT04430452
RECRUITING
PHASE2
Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCC
NCT05301842
ACTIVE_NOT_RECRUITING
PHASE3
Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant
NCT05027425
ACTIVE_NOT_RECRUITING
PHASE2
Sequential or Up-front Triple Treatment With Durvalumab, Tremelimumab and Bevacizumab for Non-resectable Hepatocellular Carcinoma (HCC) Patients
NCT05844046
RECRUITING
PHASE2
Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment
NCT03847428
ACTIVE_NOT_RECRUITING
PHASE3
Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma
NCT03937830
ACTIVE_NOT_RECRUITING
PHASE2
CTLA-4 /PD-L1 Blockade Following Transarterial Chemoembolization (DEB-TACE) in Patients With Intermediate Stage of HCC (Hepatocellular Carcinoma) Using Durvalumab and Tremelimumab
NCT03638141
COMPLETED
PHASE2
A Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in HCC
NCT06294548
RECRUITING
PHASE1/PHASE2
A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)
NCT02821754
COMPLETED
PHASE2
Durvalumab and Tremelimumab in Combination With Y-90 SIRT for Intermediate Stage HCC
NCT04522544
RECRUITING
PHASE2
A Global Study to Evaluate Transarterial Chemoembolization (TACE) in Combination With Durvalumab and Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma
NCT03778957
ACTIVE_NOT_RECRUITING
PHASE3
Durvalumab and Tremelimumab With Lenvatinib as First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma
NCT07081633
RECRUITING
PHASE2
Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab
NCT06796114
RECRUITING
NA
Immunotherapy With Durva and Treme With or Without Capecitabine in Adjuvant Treatment for Biliary Tract Cancer
NCT05239169
COMPLETED
PHASE2
TACE and SBRT Followed by Double Immunotherapy for Downstaging Hepatocellular Carcinoma
NCT04988945
RECRUITING
PHASE2
Study of Durvalumab Plus Tremelimumab as First-line Treatment in Chinese Patients With Unresectable Hepatocellular Carinoma
NCT05557838
RECRUITING
PHASE3
Study of Tremelimumab and Durvalumab (MEDI4736) (T300+D) in Advanced Hepatocellular Carcinomas With Child-Pugh-B Cirrhosis
NCT06526104
RECRUITING
PHASE2
A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE
NCT06040099
ACTIVE_NOT_RECRUITING
PHASE2
Neoadjuvant Atezo, Adjuvant Atezo + Beva Combined With RF Ablation of Small HCC: a Multicenter Randomized Phase II Trial
NCT04727307
RECRUITING
PHASE2
Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of Hepatocellular Carcinoma (HCC)
NCT01381211
TERMINATED
PHASE2
Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (MK-7902-012/E7080-G000-318/LEAP-012)
NCT04246177
ACTIVE_NOT_RECRUITING
PHASE3
A Phase I Trial of IMA970A Plus Montanide in Combination With Durvalumab (Anti-PD-L1)
NCT06218511
ACTIVE_NOT_RECRUITING
PHASE1
Himalaya Early Access Program
NCT05345678
APPROVED_FOR_MARKETING
Safety and Efficacy Study of Radioembolization in Combination With Durvalumab in Locally Advanced and Unresectable HCC
NCT04124991
COMPLETED
PHASE1/PHASE2