Patients with Hepatocellular Carcinoma MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: IMFINZI
Product Name: IMFINZI
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DURVALUMAB
Other descriptive name: IMFINZI
Concentration unit: mg/ml milligram
Sponsors
University College Dublin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients must have histopathological confirmation of hepatocellular carcinoma (HCC) prior to entering this study OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC. Fibrolamellar variant is also allowed. - Patients must have disease that is not amenable to potentially curative resection, transplantation or ablation. Patients who are BCLC stage C must have progressed on, been intolerant to, or refused prior sorafenib therapy. - Disease must be technically amenable to transhepatic arterial chemoembolization (TACE) and the provision of TACE must be considered to be a reasonable intervention as decided at the HCC tumor board at St Vincents University Hospital (SVUH). Each prospective case will be discussed at this tumor board with interventional radiology and a unanimous consensus across the disciplines of medical oncology, hepatology and interventional radiology must be reached as to the suitability of each patient for this protocol. Patients must have evaluable disease. - If liver cirrhosis is present, patient must have a Child-Pugh A/B7 classification. - Age >18 years - ECOG performance status 0-2 - Patients must have normal organ and marrow function. - Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be = grade 1 or returned to baseline. - Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers, non-invasive bladder cancer or localized prostate cancer for whom systemic therapy is not required). - Patient must be able to understand and willing to sign a written informed consent document. - 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 1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy. Subject 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: - Patients who have had standard of care chemotherapy, large field radiotherapy, or major surgery must wait 2 weeks prior to entering the study. For recent experimental therapies a 28 day period of time must elapse before treatment. - Patients who have undergone prior liver transplantation are ineligible. - Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations that would limit compliance with study requirements. - History of chronic autoimmune disease (e.g., Addison’s disease, multiple sclerosis, Graves’ disease, Hashimoto’s thyroiditis, rheumatoid arthritis, hypophysitis, etc.) with symptomatic disease within the 3 years before randomization. Note: Active vitiligo or a history of vitiligo will not be a basis for exclusion. - Dementia or significantly altered mental status that would prohibit the understanding or rendering of Information and Consent and compliance with the requirements of the protocol. - Diverticulitis either active or history of within the past 2 years. Note that diverticulosis is permitted. - Active or history of inflammatory bowel disease (colitis, Crohn’s), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener’s granulomatosis. Currently receiving immunosuppressive doses of steroids or other immunosuppressive medications (inhaled and topical steroids are permitted) - History of sarcoidosis syndrome - Patients should not be vaccinated with live attenuated vaccines within 30 days of starting durvalumab or tremelimumab treatment. - Has a known history of Human Immunodeficiency Virus (HIV). HIV-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and tremelimumab. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that tremelimumab may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events. - History of hypersensitivity reaction to human or mouse antibody products. - Pregnancy and breast feeding are exclusion factors. The effects of tremelimumab on the developing human fetus are unknown. Enrolled patients must agree to use adequate contraception prior to study entry, the duration of study participation and 6 months after the end of the treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. - Patients with unhealed surgical wounds for more than 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (in combination with TACE).;Secondary Objective: - To assess the safety of combining single-dose tremelimumab and durvalumab in patients with advanced HCC (treated with TACE). - To evaluate changes in immune parameters as well as pharmacokinetics in the peripheral blood of patients with advanced HCC undergoing TACE in combination with combined immune checkpoint inhibition. ;Primary end point(s): -6-month progression-free survival (PFS) ;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety - Overall survival time - Best Overall response rate ;Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
Ireland
Contacts
Public ContactCRC
University College Dublin
Outcome results
None listed