A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Enzalutamide in Subjects With Advanced Hepatocellular Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Enzalutamide
- Conditions
- Advanced Hepatocellular Carcinoma
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 165
- Locations
- 38
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of the study was to evaluate the efficacy of enzalutamide in participants with advanced hepatocellular carcinoma (HCC) as measured by overall survival (OS).
This study also evaluated the safety of enzalutamide; pharmacokinetics of enzalutamide and the active metabolite N-desmethyl and Progression Free Survival (PFS) of enzalutamide as compared to placebo in participants with advanced HCC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 discontinued treatment due to a drug-related toxicity. Subject may have received 1 line of systemic therapy before or after sorafenib/anti-VEGF treatment.
- •Subject has adequately recovered from toxicities due to prior HCC therapy to ≤ grade
- •Subject has an ECOG performance status ≤ 1 at Screening and on Day
- •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.
Exclusion Criteria
- •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:
Arms & Interventions
Enzalutamide 160 mg
Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Eligible participants received enzalutamide 160 mg capsules, orally QD during open label period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.
Intervention: Enzalutamide
Placebo
Participants received enzalutamide matching placebo orally, once daily (QD) during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.
Intervention: Placebo
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: From date of randomization up to data cut-off date 02 Oct 2017 (approximately 22 months); median follow-up time was 14.65 months for enzalutamide and 13.83 for placebo.
OS was defined as the time from the date of randomization until the documented date of death from any cause. Participants who were still alive at the time of the data cut-off date was censored on the last date known to be alive or at the data cutoff date, whichever occurs first. Results based on Kaplan-Meier estimates.
Secondary Outcomes
- Plasma Trough Concentrations of Enzalutamide(Predose at weeks 5, 9 and 13)
- Number of Participants With Adverse Events (AEs)(From first dose of study drug up to 30 days after last dose of study drug median (minimum, maximum) treatment duration was 64.0 (6, 1736) days for enzalutamide and 64.0 (12, 490) for placebo)
- Plasma Trough Concentrations N-desmethyl Enzalutamide (M2 Metabolite)(Predose at weeks 5, 9 and 13)
- Plasma Trough Concentrations of MDPC0001 (M1 Metabolite)(Predose at weeks 5, 9 and 13)
- Progression Free Survival (PFS)(From date of randomization up to data cut-off date 02 Oct 2017 (approximately 22 months); median follow-up time was 14.65 months for enzalutamide and 13.83 for placebo.)