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Advanced Hepatocellular CarcinomaPhase 2NCT02528643

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

A Phase 2 study testing Enzalutamide in people with Advanced Hepatocellular Carcinoma, run by Astellas Pharma Global Development, Inc. at 38 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Hepatocellular Carcinoma
What is being tested?
Enzalutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
165 participants
Where
38 sitesin 9 countries
Study dates
9 Nov 2015to 9 Feb 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 23Show fewer
  • 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:
  • 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) performed at least 6 months before Screening. Tubal ligation in the female partner of a male subject performed at least 6 months before Screening. Established and ongoing use of oral, injected, or implanted hormonal contraceptive by female partner of a male subject.
  • Female subject must not be breastfeeding at Screening or during the study period and for 3 months after final study drug administration.
  • Subject must agree not to donate sperm or ova from first dose of study drug through 3 months after the last dose of study drug.
  • Throughout the study, male subject must use a condom if having sex with a pregnant woman.
  • Subject must be able to swallow study drug and comply with study requirements.
  • Subject agrees not to participate in another interventional study while on treatment.
  • Received double-blind enzalutamide study treatment during the main study.

Who cannot join

  • 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.
Show all 44Show fewer
  • 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 bilirubin (TBL) > 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).
  • Subject has a history of bleeding esophageal varices within 3 months before the Day 1 visit.
  • Subject has a history of loss of consciousness or transient ischemic attack within 12 months before the Day 1 visit.
  • 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.
  • Subject has a gastrointestinal disorder affecting absorption.
  • 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.
  • Subject has received chemotherapy, immunotherapy or any other systemic anticancer therapy (including sorafenib) or any other investigational drug within 14 days prior to the Day 1 visit.
  • Subject has received an agent that either blocks androgen synthesis or targets the AR (e.g., abiraterone acetate, bicalutamide, enzalutamide, ARN-509 or other investigational AR signaling inhibitors). The exception of spironolactone is allowed after Medical Monitor consultation.
  • Subject has used any of the following within 28 days before the Day 1 visit:
  • 5-α reductase inhibitors
  • Systemic androgens and estrogens (vaginal estrogen creams are allowed)
  • Herbal therapies, with an antitumor effect.
  • Subject has a known history of positive test for Human Immunodeficiency Virus.
  • Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of the enzalutamide capsule components, including caprylocaproyl polyoxylglycerides (Labrasol), butylated hydroxyanisole and butylated hydroxytoluene.
  • Subject has addictive/substance abuse problems.
  • 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, places the subject at undue risk or complicates the interpretation of safety data.
  • Received double-blind placebo during the main study.

Trial locations and contacts

38 sites in 9 countries.

38 sites in 9 countries

United States8 sites

  • Site US10021

    Lebanon, New Hampshire, 03756-1000

  • Site US10016

    Milwaukee, Wisconsin, 53226-3522

  • Site US10017

    Minneapolis, Minnesota, 55455-0362

  • Site US10014

    Philadelphia, Pennsylvania, 19104

  • Site US10019

    Philadelphia, Pennsylvania, 19104

  • Site US10008

    Portland, Oregon, 97239

  • Site US10003

    San Francisco, California, 94115

  • Site US10009

    Skokie, Illinois, 60077

Other trials in United States

Italy6 sites

  • Site IT39005

    Benevento

  • Site IT39002

    Milan, 20132

  • Site IT39006

    Milan, 20122

  • Site IT39011

    Padova, 35128

  • Site IT39004

    Pavia, 27100

  • Site IT39008

    Rozzano, Milan, 20089

Other trials in Italy

South Korea6 sites

  • Site KR82002

    Seongnam-si, Gyeonggi-do, 013620

  • Site KR82005

    Seoul, Seoul Teugbyeolsi, 135-710

  • Site KR82006

    Seoul, 03080

  • Site KR82007

    Seoul, 03722

  • Site KR82004

    Seoul, 05505

  • Site KR82001

    Seoul, 06591

Other trials in South Korea

United Kingdom5 sites

  • Site GB44007

    Birmingham, B15 2WB

  • Site GB44004

    London, SE5 9RS

  • Site GB44008

    London, W12 OHS

  • Site GB44005

    Manchester, M20 4BX

  • Site GB44002

    Metropolitan Borough of Wirral, CH63 4JY

Other trials in United Kingdom

Taiwan4 sites

  • Site TW88603

    Douliu, 640

  • Site TW88606

    Tainan, 704

  • Site TW88605

    Tainan, 710

  • Site TW88604

    Taipei, 10048

Other trials in Taiwan

Canada3 sites

  • Site CA15002

    Montreal, Quebec, H3T 1E2

  • Site CA15003

    Montreal, H4A 3J1

  • Site CA15001

    Toronto, Ontario, M5G2C4

Other trials in Canada

Spain3 sites

  • Site ES34003

    Barcelona, 08035

  • Site ES34006

    Córdoba, 14004

  • Site ES34004

    Madrid, 28222

Other trials in Spain

Hong Kong2 sites

  • Site HK85202

    Kowloon, 999077

  • Site HK85204

    Shatin, 999077

Other trials in Hong Kong

Puerto Rico1 site

  • Site US10001

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Enzalutamide in Subjects With Advanced Hepatocellular Carcinoma

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.

Being tested
Enzalutamide, Placebo
Keywords
MDV3100, advanced hepatocellular carcinoma, enzalutamide, Xtandi, ASP9785

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnzalutamideDrug

    Also called MDV3100, Xtandi

    Oral capsule

  • PlaceboDrug

    Oral capsule

Study groups in NCT02528643
Study groupRoleWhat they receive
Enzalutamide 160 mgExperimentalParticipants 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.
Receives: Drug: Enzalutamide
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Number of Participants With Adverse Events (AEs)

    Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug or initiation of new treatment, whichever comes first. AEs were considered as serious if resulted in in death, was life-threatening resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly or birth defect, required inpatient hospitalization or led to prolongation of hospitalization and other medically important events.

    Measured: 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

  2. Plasma Trough Concentrations of Enzalutamide

    Blood samples were collected for analysis.

    Measured: Predose at weeks 5, 9 and 13

  3. Plasma Trough Concentrations N-desmethyl Enzalutamide (M2 Metabolite)

    Blood samples were collected for analysis.

    Measured: Predose at weeks 5, 9 and 13

  4. Plasma Trough Concentrations of MDPC0001 (M1 Metabolite)

    Blood samples were collected for analysis.

    Measured: Predose at weeks 5, 9 and 13

  5. Progression Free Survival (PFS)

    PFS was 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 as determined by the investigator or death from any cause on study, whichever occurred first. The earliest of the censoring times was used: Participants with (1) no evaluable postbaseline imaging assessments or did not die were censored at the randomization date; (2) no radiographical progression or did not die before analysis cutoff date were censored at the last radiological assessment date before analysis cutoff date; (3) with no radiographical progression or did not die before new HCC treatment was censored at the last radiological assessment date before start of new HCC treatment. Based on Kaplan-Meier.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2015 (estimated)
  2. Study start9 Nov 2015
  3. Primary completion2 Oct 2017
  4. Study completion9 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
165 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02528643
Sponsor's protocol ID
9785-CL-3021
Other IDs
2014-004283-37, 2014
Status last verified
Nov 2024
First submitted
18 Aug 2015
Last updated
6 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • 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.

    PubMed 34351608

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enzalutamide in people with Advanced Hepatocellular Carcinoma, run by Astellas Pharma Global Development, Inc. at 38 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Italy, South Korea, United Kingdom, Taiwan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02528643, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2024.

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