Status and phase
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Treatments
About
The objective of the ROWAN clinical study is to assess the efficacy of local tumor control in HCC patients who receive TheraSphere followed by durvalumab and tremelimumab.
Full description
A global open-label, prospective, multi-center Phase II trial designed to assess the safety and efficacy of TheraSphere administered before initiation of Durvalumab with Tremelimumab in HCC patients who are not a candidate for resection, thermal ablation or liver transplant at the time of study entry.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Participants must be aged ≥18 years at the time of screening.
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.
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
Measurable disease by mRECIST criteria (e.g. ≥10mm of enhancement).
Tumor volume ≤35% of whole liver volume (determined by imaging).
Future liver remnant volume (FLRV) ≥30% of whole liver volume. FRLV is the volume of liver not planned to be treated with TheraSphere and free of HCC.
Dosimetry criteria for tumor(s) and normal tissue can be determined.
Patients with previous liver resection or ablation ≥6 months from end of previous treatment to TheraSphere administration.
Previous transarterial chemoembolization (TACE) is permitted if:
Patients with portal vein thrombosis (PVT) Vp0, Vp1, or Vp2.
Patients with HBV or HCV infection are to have documented virology status of hepatitis as confirmed by HBV and HCV serology test:
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/uL
Negative serum pregnancy test in females of childbearing potential.
Adequate contraception for the patient and his/her sexual partner.
Adequate renal and marrow function as defined below:
Absolute lymphocyte count ≥0.5 X 109/L
Adequate liver function, as defined by
Body weight >30 kg and BMI ≥18 kg/m2.
Exclusion criteria
Any contraindication to angiography or selective visceral catheterization.
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.
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.
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]):
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)).
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 inclusion in this study
Hepatic encephalopathy present at study entry and/or episodes of encephalopathy (Grade ≥ 2) within 6 months prior to study inclusion.
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% (Roussos & Koutsoukou, 2003) 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 #18).
Active or prior documented autoimmune or inflammatory disorders (including but not limited to, 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, etc]). The following are exceptions to this criterion:
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
History of gastrointestinal bleeding 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 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.
History of malignancy, other than HCC, within three years, except the condition is one of the following:
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 tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), HBV and HVC co-infection, HBV and Hep D co-infection, human immunodeficiency virus (HIV 1/2 antibodies) plus HCV or HBV co-infection.
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 are not able to follow the TheraSphere, durvalumab or tremelimumab treatment requirements.
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:
Primary purpose
Allocation
Interventional model
Masking
100 participants in 1 patient group
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Central trial contact
Patrice Feaster; Maile Krumpschmidt, MD
Data sourced from clinicaltrials.gov
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