hepatocellular carcinoma
Conditions
Interventions
administration of study drug (Durvalmab, Tremelimumab) and parforming of carbon ion radiotherapy (CIRT)
CohortA
administration of Durvalmab and parforming CIRT
CohortB
administration of Durvalmab a
Sponsors
Ogasawara Sadahisa
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. For patients aged >=20 years and enrolling, a written informed consent should be obtained from the patient and his or her legally acceptable representative. 2.Age >=20 years at time of study entry 3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4.Body weight >30 kg 5.Adequate normal organ and marrow function as defined below: Haemoglobin >=9.0 g/dL Absolute neutrophil count (ANC) > 1500 per mm3 Platelet count >=75 x 109/L (>=75,000 per mm3) Serum bilirubin =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: 6.Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 7.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. 8.Advanced HCC confirmed histologically or by the typical findings of a hypervascular tumor on computed tomography or angiography 9.(CohortA and CohortB) Refractory or unbearable forsystemic therapies for advanced HCC (including atezolizumab conbined with bevacizumab, sorafenib, lenvatinib) (exclution of expantion cohort) 10.Must not be eligible for locoregional therapy for unresectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed >=28 days prior to the baseline scan for the current study. Acceptable locoregional therapy for HCC are Ethanol Infusion Therapy, Radio Wave ablation Therapy, Transcatheter Arterial chemoembolization (TACE), Transcatheter arterial infusion (TAI). Hepatic Arterial Infusion Chemotherapy (HAIC) is not allowed. 11.Patients who have been diagnosed with HCC showing MVI. MVI is defined as a tumor thrombus in the major hepatic and/or portal vein branches (Vp2, Vp3, Vp4, Vv2, and Vv3) identifi
Exclusion criteria
Exclusion criteria: 1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2.Participation in another clinical study with an investigational product during the last 4 weeks, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 3.Any unresolved toxicity NCI CTCAE Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria Patients with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. 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. 4.Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 5.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. 6.History of allogenic organ transplantation. 7.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: Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study physician Patients with celiac disease controlled by diet alone 8.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 9.History of another primary malignancy except for 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 Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease 10.History of leptomeningeal carcinomatosis 11.History of, or current, 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. 12.Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >=470 ms 13.History of active primary immunodeficiency 14.Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV). HBV positive (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA); HCV positive (presence of anti-HCV a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AEs/SAEs including DLTs | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS), Survival Rate at 6 months, Objective Response Rate (ORR), Progression Free Survival (PFS) at 6 months (in accordance with mRECIST), and if appropriate, Time to Progression (TTP). | — |
Contacts
Public ContactAsahi Takahashi
Chiba University hospital
Outcome results
None listed