A Phase 2 Study of Tremelimumab (Day 1 only), Durvalumab (MEDI4736) and Trans-arterial catheter chemoembolization (TACE)in patients with advanced Hepatocellular Carcinoma (HCC)
- Conditions
- Advanced Hepatocellular Carcinoma (HCC)Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-510117-26-00
- Lead Sponsor
- niversity College Dublin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 29
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. No prior systemic therapy for advanced HCC is permitted, though investigator discretion is allowed for patients who discontinued sorafenib/lenvatinib for tolerability reasons, Body weight >30kg, Patients must have normal organ and marrow function as defined below: o Haemoglobin =9.0 g/dL o Absolute neutrophil count (ANC =1.0 × 109 /L) o Platelet count =75 × 109/L o Serum bilirubin =1.5 x institutional upper limit of normal (ULN). <> o AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN o Measured creatinine clearance (CL) >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:, ? Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be = grade 1 or returned to baseline., 13.Men and women of all races and ethnic groups are eligible for this trial., ? 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 <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). - 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. 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, Patients must have HCC with evidence of extrahepatic disease that is not amenable to potentially curative resection, transplantation or ablation. Staging as per BCLC group C., 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 GI MDT at the Mater Misericordiae University Hospital (MMUH). Each prospective case will be discussed at this tumor board with interventional radiology and a unanimous consensus ac
Patients who have had standard of care chemotherapy, large field radiotherapy, or major surgery must wait 4 weeks prior to entering the study., 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 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 consentHistory 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). Active or history of systemic lupus erythematosus or Wegener’s granulomatosis., Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:, Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent, ? Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)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. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Adjust wording as necessary and consider evaluating at screening for studies with known hepatotoxicity or other relevant requirements., History of hypersensitivity reaction to human or mouse antibody products., Pregnancy and breast feed
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the 6-month progression-free survival (PFS) of tremelimumab (Day 1 only) and durvalumab in patients with advanced, metastatic HCC following treatment with TACE;Secondary Objective: To assess the safety of combining single-dose tremelimumab, durvalumab and TACE in patients with advanced HCC, To determine the response rate (RR) and overall survival (OS) of tremelimumab (Day 1 only), durvalumab and TACE in patients with advanced, metastatic HCC;Primary end point(s): 6-month Progression-free survival (PFS) with median PFS included in statistical analysis
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Safety;Secondary end point(s):Overall survival time;Secondary end point(s):Best overall response rate;Secondary end point(s):EXPLORATORY ENDPOINT: Changes in immune parameters in the peripheral blood over time