A study to assess the safety and effectiveness of enzalutamide in patients with advanced hepatocellular carcinoma
- Conditions
- Male and female subjects with HCC of any etiology who have progressed on or were intolerant to sorafenib or other anti-VEGF therapy in the advanced setting.MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004283-37-IT
- Lead Sponsor
- ASTELLAS PHARMA GLOBAL DEVELOPMENT, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 144
- Subject is = 18 years of age, or is considered an adult according to local regulation at the time of signing informed consent;
- Subject has a documented diagnosis of advanced HCC of any etiology.
- Subject has BCLC stage B or C;
- Subject’s lesions are not amenable to local therapies which may be beneficial, such as transarterial chemoembolization (TACE), radiofrequency ablation, radiotherapy, etc., and the subject is not a candidate for any curative treatments such as resection or liver transplant;
- Subject has hepatic function status of Child Pugh Class A at Screening;
- Subject received prior systemic treatment for HCC with sorafenib or other anti-VEGF therapy and had confirmed disease progression or had discontinued treatment due to a drug-related toxicity. Subject may have received 1 line of systemic investigational therapy before or after sorafenib/anti-VEGF treatment;
- Subject has adequately recovered from toxicities due to prior HCC therapy to = grade 1;
- Subject has an ECOG performance status = 1 at Screening and on Day 1;
- Subject has available formalin-fixed, paraffin-embedded tumor specimen with adequate viable tumor cells in a tissue block or unstained serial slides accompanied by an associated pathology report prior to enrollment. Archival or fresh biopsy tissue is required;
- Subject has an estimated life expectancy of at least 3 months on Day 1, in the opinion of the Investigator.
- Female subject is either: -->Not of childbearing potential: ---> postmenopausal (defined as no spontaneous menses for at least 12 consecutive months prior to Screening with follicle stimulating hormone [FSH] > 40 IU/L for women < 55 years of age at Screening), or ---> documented to be surgically sterile or status posthysterectomy (at least 1 month prior to Screening). --> Or, if of childbearing potential: ---> must have a negative urine pregnancy test at Screening and on Day 1 before the first dose of study drug is administered, and ---> must use 2 acceptable methods of birth control* if sexually active from Screening through 3 months after the last dose of study drug.
[...]
Open-Label Period additional Inclusion Criteria:
- Received double-blind enzalutamide study treatment during the main study.
The full list of inclusion criteria is available in the protocol synopsis.
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 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 72
- Subject has a severe concurrent disease, infection or comorbidity that, in the judgment of the investigator, would make the subject inappropriate for enrollment;
- Subject has fibrolamellar variant of HCC;
- Subject has status of Child Pugh Class B or C at Screening;
- Subject has a history of organ allograft including liver transplant;
- Subject has uncontrolled symptomatic ascites;
- Subject has known or suspected brain metastasis or active leptomeningeal disease;
- Subject has a history of a non-HCC malignancy with the following exceptions:
¿The subject with a previous history of a noninvasive carcinoma is eligible if in the opinion of the investigator he/she has had successful curative treatment any time prior to Screening and requires no further therapy for the malignancy.
¿For all other malignancies, the subject is eligible if he/she has undergone potentially curative therapy and has been considered disease free for at least 3 years prior to Screening.
-Subject has inadequate marrow, hepatic, and/or renal function at the Screening Visit defined as:
¿Absolute neutrophil count < 1.5 x109/L (< 1500 cells/mm3)
¿Platelet count < 50 x109/L (< 50,000 cells/mm3)
¿Hemoglobin < 8.5 g/dL (< 5.3 mmol/L)
¿International normalized ratio > 1.7
¿Albumin < 2.8 g/dL (< 28 g/L)
¿Total bilirubinTBL > 2 x ULN
¿AST or ALT > 5 x ULN
¿Creatinine > 1.5 x ULN
Note: Transfusions/infusions to meet eligibility criteria are not allowed but if in the opinion of the Principal Investigator, it is beneficial, the patient may be rescreened after receiving one of these procedures.
- Subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma, encephalopathy within 3 months of Day 1).
[...]
Open-Label Period Exclusion Criteria:
- Received double-blind placebo during the main study
- Subject has met discontinuation criteria during the main study
- Subject has any other condition or reason that, in the opinion of the Investigator, interferes with the ability of the subject to participate in the trial or places the subject at undue risk
The full list of exclusion criteria is available in the protocol synopsis.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of enzalutamide in subjects with advanced hepatocellular carcinoma (HCC) as measured by overall survival (OS).;Secondary Objective: To evaluate:<br>- the safety of enzalutamide in subjects with advanced HCC;<br>- the pharmacokinetics (PK) of enzalutamide and the active metabolite N-desmethyl enzalutamide in subjects with advanced HCC;<br>- the Progression Free Survival (PFS) of enzalutamide as compared to placebo in subjects with advanced HCC.;Primary end point(s): The primary efficacy variable is overall survival (OS).;Timepoint(s) of evaluation of this end point: OS is defined as the time from the date of randomization until date of death from any cause.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Safety Endpoints:<br>The safety of enzalutamide will be assessed on an ongoing basis by evaluation of AEs/serious adverse events, clinical safety laboratory tests, vital signs, and other safety measures. <br>Pharmacokinetic Endpoints:<br>Predose plasma concentrations of enzalutamide and N-desmethyl enzalutamide will be analyzed.<br>Efficacy Endpoints:<br>- Time to Progression (TTP);<br>- Progression Free Survival (PFS).;Timepoint(s) of evaluation of this end point: Efficacy Endpoints:<br>- TTP, defined as the time from the date of randomization until the date of the first radiographically documented disease progression as assessed by the investigator.<br>- FS, defined as the time from the date of randomization until the date of documented radiographic disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause on study, whichever occurs first as assessed by the investigator.