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 settingMedDRA version: 18.1Level: 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-ES
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 165
Waivers to the inclusion and exclusion criteria will NOT be allowed.
1. Subject has consented and signed an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC) approved written Informed Consent and privacy language as per national
regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] for U.S. sites)
prior to any study-related procedures (including withdrawal of prohibited medication, if
applicable).
2. Subject is ? 18 years of age.
3. Subject has histological diagnosis of advanced HCC of any etiology. Clinical diagnosis by the
European Association for the Study of the Liver (EASL) criteria is acceptable. For subjects
without cirrhosis, histological confirmation is required (archive samples are acceptable).
4. Subject has BCLC stage B or C.
5. Subject?s lesions are not amenable to local therapies which may be beneficial, such as
transarterial chemoembolization (TACE), radiofrequency ablation, etc., and the subject is not a
candidate for any curative treatments such as resection or liver transplant.
6. Subject has hepatic function status of Child Pugh Class A at Screening.
7. Subject received prior systemic treatment for HCC with sorafenib or other anti-VEGF therapy
and had confirmed disease progression or discontinued treatment due to a drug-related toxicity.
Subject may have received 1 line of systemic investigational therapy after sorafenib/anti-VEGF
treatment.
8. Subject has adequately recovered from toxicities due to prior HCC therapy to ? grade 1.
9. Subject has an ECOG performance status ? 1 at Screening and on Day 1.
10. Subject has available formalin-fixed, paraffin-embedded tumor specimen that enabled the
diagnosis of HCC with adequate viable tumor cells in a tissue block (preferred) or ? 10
(20 preferred) unstained serial slides accompanied by an associated pathology report is required
prior to enrollment. Archival or fresh biopsy tissue is acceptable.
11. Subject has an estimated life expectancy of at least 3 months on Day 1, in the opinion of the
investigator
12. 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* from Screening through 3 months after the last dose of study drug.
13. Male subject and his female partner who is of childbearing potential must use 2 acceptable
methods of birth control from Screening through 3 months after the last dose of study drug.
*Two acceptable methods of birth control are as follows:
? Condom (barrier method of contraception);
AND
? One of the following is required:
- Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female subject or female partner of a male subject;
- Additional barrier method: contraceptive sponge or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female subject or female partner of a male subject.
- For male subject or male partner of female subject, vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy)
1. Subject has a severe concurrent disease, infection or comorbidity that, in the judgment of the
investigator, would make the subject inappropriate for enrollment.
2. Subject has fibrolamellar variant of HCC.
3. Subject has status of Child-Pugh Class B or C at Screening.
4. Subject has a history of organ allograft including liver transplant.
5. Subject has uncontrolled symptomatic ascites.
6. Subject has known or suspected brain metastasis or active leptomeningeal disease.
7. 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.
8. 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 bilirubin > 2 x ULN
-AST or ALT > 5 x ULN
-Creatinine > 1.5 x ULN
9. 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).
10. Subject has a history of esophageal varices within 3 months before the Day 1 visit.
11. Subject has a history of loss of consciousness or transient ischemic attack within 12 months
before the Day 1 visit.
12. Subject has clinically significant cardiovascular disease including:
-Myocardial infarction within 6 months before the Day 1 visit.
-Uncontrolled angina within 6 months before the Day 1 visit.
-Congestive heart failure New York Heart Association (NYHA) Class III or IV or history of
congestive heart failure NYHA Class III or IV in the past, unless a Screening echocardiogram
or multi-gated acquisition scan performed within 3 months before the Day 1 visit reveals a
left ventricular ejection fraction that is ? 45%.
- History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsade de Pointes).
-History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
- Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive measurements at the Screening visit.
-Bradycardia (in the presence of known cardiovascular disease) as indicated by a heart rate of
< 50 beats per minute on the Screening electrocardiogram (ECG) recording.
-Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the Screening visit.
13. Subject has a gastrointestinal disorder affecting absorption.
14. Subject had previous local therapy (e.g., surgery, radiation therapy, hepatic arterial therapy,
chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation)
within 14 days prior to Day 1, has not recovered from toxicities from prior local therapy or may
require major surgical procedure during the course of the study.
15. Subject has received chemotherapy, immunotherapy or any other systemic anticancer therapy
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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 Time to Progression (TTP) and 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<br>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<br>radiographically documented disease progression as assessed by the investigator.<br>? PFS, defined as the time from the date of randomization until the date of documented<br>radiographic disease progression according to Response Evaluation Criteria in Solid Tumors<br>(RECIST) 1.1 or death from any cause on study, whichever occurs first as assessed by the<br>investigator.