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)

Phase 1

Recruiting

• Conditions: Hepatocellular Carcinoma; MedDRA version: 21.1Level: LLTClassification code: 10049010Term: Carcinoma hepatocellular Class: 10029104; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: CTIS2023-508945-41-00
• Lead Sponsor: Biocompatibles UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-18
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified