BridgeMD
A clinical study to assess how safe and effective it is for subjects with hepatocellular carcinoma (HCC) to receive radiation therapy with TheraSphere followed by immunotherapy (durvalumab and tremelimumab treatment)
EU CTIS ID: 2023-508945-41-00
What this study is testing
To assess the efficacy of treatment with TheraSphere followed by durvalumab and tremelimumab in HCC patients
- 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
- Participants must be aged ≥18 years at the time of screening.
- Adequate renal and marrow function as defined below: a. Hemoglobin (Hgb) ≥9.0 g/dL b. Absolute neutrophil count (ANC) ≥1.0 x 109/L c. Platelet count ≥50 x 109/L d. Measured or calculated creatinine clearance ≥40 mL/min as determined by Cockcroft-Gault (using actual body weight)
- Absolute lymphocyte count ≥0.5 X 109/L
- Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] data privacy regulations in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Adequate liver function, as defined by a. Child-Pugh A b. Albumin-bilirubin (ALBI) score ≤ -2 with upper limit for(i.e., ALBI score ≤ -grade 1 and subset of ALBI grade 2.). Patients with confirmed Gilbert’s syndrome may not have an evaluable bilirubin value; therefore, ALBI score should not be considered for such patients. Patients with Gilbert’s syndrome will be eligible with any bilirubin value, as long as Albumin level is ≥ 34 g/L. . c. AST and ALT <3 x ULN
- Body weight >30 kg and BMI ≥18 kg/m2.
You likely can't join if
- Any contraindication to angiography or selective visceral catheterization.
- Concurrent treatment for HCC or treatment in the last 4 weeks in another clinical study, unless it is an observational study (non-interventional) or during a non-interventional follow-up stage of an interventional study, or prior to inclusion in this study.
- HCC with infiltrative disease that is not evaluable by mRECIST.
- Pulmonary insufficiency (defined by an arterial oxygen pressure (PaO2) of <60 mmHg, or oxygen saturation (SaO2) of <90% or clinically evident chronic obstructive pulmonary disease (COPD).
- Medical history of radiation pneumonitis or recent pneumonitis, regardless of causality
- History of any organ allograft, including bone marrow allo and autograft.
See the full eligibility criteria
Who can join
- Participants must be aged ≥18 years at the time of screening.
- Adequate renal and marrow function as defined below: a. Hemoglobin (Hgb) ≥9.0 g/dL b. Absolute neutrophil count (ANC) ≥1.0 x 109/L c. Platelet count ≥50 x 109/L d. Measured or calculated creatinine clearance ≥40 mL/min as determined by Cockcroft-Gault (using actual body weight)
- Absolute lymphocyte count ≥0.5 X 109/L
- Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] data privacy regulations in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Adequate liver function, as defined by a. Child-Pugh A b. Albumin-bilirubin (ALBI) score ≤ -2 with upper limit for(i.e., ALBI score ≤ -grade 1 and subset of ALBI grade 2.). Patients with confirmed Gilbert’s syndrome may not have an evaluable bilirubin value; therefore, ALBI score should not be considered for such patients. Patients with Gilbert’s syndrome will be eligible with any bilirubin value, as long as Albumin level is ≥ 34 g/L. . c. AST and ALT <3 x ULN
- Body weight >30 kg and BMI ≥18 kg/m2.
- Life expectancy ≥6 months
- HCC, diagnosed by radiographic imaging or histology
- Patient not a candidate for liver resection, thermal ablation, or transplantation at the time of study entry.
- ECOG 0 or 1
- At least one HCC lesion measurable by mRECIST criteria (e.g. ≥10 mm of enhancement).
- Dosimetry criteria for tumor(s) and normal tissue can be determined. Please refer to Supplement B for further details
- Tumor volume ≤35% of whole liver volume (determined by imaging).
- Future remnant liver volume (FRLV) ≥30% of whole liver volume. FRLV is the volume of liver not planned to be treated with TheraSphere and free of HCC.
- Patients that have had previous ascites/encephalopathy episodes should be free of symptoms and of supportive treatment (lactulose or equivalent, diuretics) at study entry.
- Patients with previous liver resection or ablation ≥6 months from end of previous treatment to TheraSphere administration
- Previous transarterial chemoembolization (TACE) is permitted if: a. Previous TACE performed ≥8 months before TheraSphere administration and b. Result of previous TACE was CR and c. Current tumor is not a recurrence of previously treated lesion
- Patients with no portal vein thrombosis (PVT) Vp0, OR patients with Vp1, or Vp2 are eligible Refer to Protocol Appendix F for details regarding PVT classification.
- Patients with HBV or HCV infection must have documented HBV deoxyribonucleic acid (DNA) or HCV ribonucleic acid (RNA)status and appropriate treatment must be provided as follows a. HBV DNA ≥10 IU/mL (or above the limit of detection per local laboratory): Patient must receive antiviral therapy per institutional practice. Patients must show evidence of HBV stabilization or signs of viral response (e.g., reduction HBV DNA levels) prior to enrollment. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. b. HBV DNA <10 IU/mL (or under the limit of detection per local laboratory): Patients do not require antiviral therapy. These patients will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/mL or above the limit of detection per local laboratory). Patients with detectable HBV DNA during the study must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. c. Detectable HCV RNA: Patients with active HCV infection must be managed per local institutional practice for the study duration.
- Patients with Human Immunodeficiency Virus (HIV) infection are eligible, provided the HIV infection is well controlled with no current or previous AIDS-related complications and CD4+ T-cell (CD4+) counts ≥ 350 cells/μL
- Negative urine/serum pregnancy test in females of childbearing potential
- Adequate contraception for the patient and his/her sexual partner.
What rules you out
- Any contraindication to angiography or selective visceral catheterization.
- Concurrent treatment for HCC or treatment in the last 4 weeks in another clinical study, unless it is an observational study (non-interventional) or during a non-interventional follow-up stage of an interventional study, or prior to inclusion in this study.
- HCC with infiltrative disease that is not evaluable by mRECIST.
- Pulmonary insufficiency (defined by an arterial oxygen pressure (PaO2) of <60 mmHg, or oxygen saturation (SaO2) of <90% or clinically evident chronic obstructive pulmonary disease (COPD).
- Medical history of radiation pneumonitis or recent pneumonitis, regardless of causality
- History of any organ allograft, including bone marrow allo and autograft.
- History of active primary/acquired immunodeficiency, that makes patients unsuitable for additional immunotherapy in this study (per investigator and as detailed in exclusion criterion #17).
- Active or prior documented autoimmune or inflammatory disorders (including but not limited to auto immune hepatitis, inflammatory bowel disease [e.g. ulcerative colitis or Crohn’s disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis]). The following are exceptions to this criterion a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (e.g. following Hashimoto’s syndrome) stable on hormone replacement therapy c. Any chronic skin condition that does not require systemic therapy. d. Patients without active disease in the last 5 years may be included but only after consultation with the Sponsor Study physician. e. Patients with celiac disease controlled by diet alone
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection) b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. c. Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication).
- History of gastrointestinal bleeding (GI) within 42 days prior to study inclusion, active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device). Patients with gastrointestinal bleeding related to portal hypertension that cannot be controlled with a non-selective betablocker. Patients with known varices that have not bled or which have been clinically addressed can enter the study. No endoscopic exploration is required before study inclusion.
- Presence of biliary stent or sphincterotomy within one year prior to study inclusion
- Cone Beam CT (CBCT) or Technetium-99m macroaggregated Albumin (99mTc-MAA) hepatic arterial perfusion scintigraphy shows any deposition to the gastrointestinal tract that may not be corrected by angiographic techniques.
- History of malignancy, other than HCC, within three years, except the condition is one of the following: a. Adequately treated carcinoma in situ of the cervix, early squamous cell carcinoma or basal cell carcinoma of the skin, localized prostate cancer, breast ductal carcinoma in situ, or low-grade endometrial carcinoma with no myometrial invasion b. Localized prostate cancer under active surveillance. c. Other cancer when there is a negligible risk of recurrence or progression or death (5-year OS rate > 90%).
- Major surgical procedure (as defined by the Investigator) within 42 days prior to study inclusion
- A history of severe allergy or intolerance to contrast agents, narcotics, sedatives, or atropine that cannot be managed medically
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients that cannot be managed medically
- Active infection, including: a. Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), b. HBV and HCV co-infection, c. HBV and Hep D co-infection, d. Human immunodeficiency virus (HIV 1/2 antibodies) plus HCV or HBV coinfection.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab and/or tremelimumab. Note: patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and/or tremelimumab and up to 30 days after the last dose of durvalumab and/or tremelimumab
- Female patients who are pregnant or breastfeeding and who do not want to stop breastfeeding. Male or female patients of reproductive potential who are not willing to employ any effective birth control method from screening and for at least 90 days after TheraSphere administration, 90 days after the last dose of durvalumab, and 6 months after the last dose of tremelimumab.
- Unstable chronic disease or evidence of any disease or condition that would place the patient at undue risk and preclude safe use of TheraSphere, durvalumab and tremelimumab treatment as deemed by the site principal investigator. Patients who have stable respiratory disease adequately treated with medication are not excluded, for example COPD.
- Patients who are not able to follow the TheraSphere, durvalumab or tremelimumab treatment requirements.
- Patients that have had previous ascites/encephalopathy episode should be free of symptoms and of supportive treatment (lactulose or equivalent, diuretics) at study entry.
- 99mTc-MAA hepatic arterial perfusion scintigraphy shows poor tumor and/or portal vein thrombosis (PVT) targeting that would lead to a dose that does not meet the liver dosing criteria. Please refer to Supplement B for further details
- For France Patients Only Persons deprived of their liberty by a judicial or administrative decision, persons subject to psychiatric care under articles L. 3212-1 and L. 3213-1 who are not covered by the provisions of Article L. 1121-8 and persons admitted to a health or social establishment for purposes other than research, including: a. Pregnant, parturient, breast-feeding women (see also inclusion criterion 16 and exclusion criterion 27) b. Minors (see also inclusion criterion 1) c. Persons receiving psychiatric treatment (see also exclusion criteria 28) d. Persons admitted to a health or social establishment for purposes other than research e. Person of full age under curatorship f. Adult subject to a mandate for future protection, a family authorization, or a guardianship measure g. Person not affiliated or not beneficiary of a social security scheme
- Shunting of blood to the lungs that could result in delivery of >30 Gy to the lungs in a single treatment, or >50 Gy cumulative dose to the lungs in case of multiple TheraSphere treatments, as seen on 99mTc-MAA hepatic arterial perfusion scintigraphy.
- Vp3, Vp4, hepatic vein invasion, or inferior vena cava (IVC) invasion
- Extrahepatic metastases (patients with extrahepatic spread [EHS]): a. EHS is any extrahepatic lesion that, according to clinical symptoms, histology, or radiological imaging data, is highly suspicious of being metastases. b. For patients with bone pain/neurological symptoms (deficit, seizure or else) at baseline and suspected of metastases at screening, a bone scan/brain MRI is recommended prior to study entry. c. Extrahepatic nontarget non-measurable lesions (<1 cm per RECIST 1.1) are acceptable if considered not suspicious by the investigator.
- Any previous systemic HCC treatment
- Prior exposure to immune mediated therapy for other disease, such as other anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CTLA-4, antibodies, etc
- Previous liver radiation (external beam radiation therapy (EBRT) or peptide receptor radionuclide therapy (PRRT) or selective internal radiation therapy (SIRT).
The study team makes the final eligibility decision.
Where it's taking place
- Switzerland
- United States
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.
Where is this trial taking place?
Study sites include Switzerland; United States. Enter your location above to see the nearest site and check your eligibility.
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.