A Study to Assess the Efficacy and Safety of Enzalutamide in Subjects With Advanced Hepatocellular Carcinoma

NCT02528643 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 9785-CL-30212014-004283-37
• Study Type: interventional
• Target: 165
• Locations: 9 countries
• Sites: 38

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.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

MDV3100; advanced hepatocellular carcinoma; enzalutamide; Xtandi; ASP9785

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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.

  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.

Secondary Outcomes (5)

• 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 of Enzalutamide

  Predose at weeks 5, 9 and 13

• 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.

Study Arms (2)

Enzalutamide 160 mg

EXPERIMENTAL

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.

Drug: Enzalutamide

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Enzalutamide DRUG

Oral capsule

Also known as: MDV3100, Xtandi

Enzalutamide 160 mg

Placebo DRUG

Oral capsule

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• Sexually active 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:

You may not qualify if:

• 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)

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Pfizer: collaborator

Study Sites (38)

Site US10003

San Francisco, California, 94115, United States

Location

Site US10009

Skokie, Illinois, 60077, United States

Location

Site US10017

Minneapolis, Minnesota, 55455-0362, United States

Location

Site US10021

Lebanon, New Hampshire, 03756-1000, United States

Location

Site US10008

Portland, Oregon, 97239, United States

Location

Site US10014

Philadelphia, Pennsylvania, 19104, United States

Location

Site US10019

Philadelphia, Pennsylvania, 19104, United States

Location

Site US10016

Milwaukee, Wisconsin, 53226-3522, United States

Location

Site CA15001

Toronto, Ontario, M5G2C4, Canada

Location

Site CA15002

Montreal, Quebec, H3T 1E2, Canada

Location

Site CA15003

Montreal, H4A 3J1, Canada

Location

Site HK85202

Kowloon, 999077, Hong Kong

Location

Site HK85204

Shatin, 999077, Hong Kong

Location

Site IT39008

Rozzano, Milan, 20089, Italy

Location

Site IT39005

Benevento, Italy

Location

Site IT39002

Milan, 20132, Italy

Location

Site IT39006

Milan, 20122, Italy

Location

Site IT39011

Padua, 35128, Italy

Location

Site IT39004

Pavia, 27100, Italy

Location

Site US10001

San Juan, 00927, Puerto Rico

Location

Site KR82002

Seongnam-si, Gyeonggi-do, 013620, South Korea

Location

Site KR82005

Seoul, Seoul Teugbyeolsi, 135-710, South Korea

Location

Site KR82006

Seoul, 03080, South Korea

Location

Site KR82007

Seoul, 03722, South Korea

Location

Site KR82004

Seoul, 05505, South Korea

Location

Site KR82001

Seoul, 06591, South Korea

Location

Site ES34003

Barcelona, 08035, Spain

Location

Site ES34006

Córdoba, 14004, Spain

Location

Site ES34004

Madrid, 28222, Spain

Location

Site TW88603

Douliu, 640, Taiwan

Location

Site TW88606

Tainan, 704, Taiwan

Location

Site TW88605

Tainan, 710, Taiwan

Location

Site TW88604

Taipei, 10048, Taiwan

Location

Site GB44007

Birmingham, B15 2WB, United Kingdom

Location

Site GB44004

London, SE5 9RS, United Kingdom

Location

Site GB44008

London, W12 OHS, United Kingdom

Location

Site GB44005

Manchester, M20 4BX, United Kingdom

Location

Site GB44002

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Related Publications (1)

• Ryoo BY, Palmer DH, Park SR, Rimassa L, Debashis Sarker, Daniele B, Steinberg J, Lopez B, Lim HY. Efficacy and Safety Results from a Phase 2, Randomized, Double-Blind Study of Enzalutamide Versus Placebo in Advanced Hepatocellular Carcinoma. Clin Drug Investig. 2021 Sep;41(9):795-808. doi: 10.1007/s40261-021-01063-0. Epub 2021 Aug 5.

  PMID: 34351608 DERIVED

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website.
• Link to plain language summary of the study on the Trial Results Summaries website.

MeSH Terms

Interventions

enzalutamide

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 19, 2015
• Study Start: November 9, 2015
• Primary Completion: October 2, 2017
• Study Completion: February 9, 2021
• Last Updated: December 6, 2024
• Results First Posted: November 20, 2018

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); KR (6); HK (2); TW (4); CA (3); IT (6); US (8); GB (5); ES (3)