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

NCT02528643

Last updated date
Study Location
Site US10003
San Francisco, California, 94115, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Advanced Hepatocellular Carcinoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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:

- 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.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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 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.

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Advanced Hepatocellular CarcinomaA Study to Assess the Efficacy and Safety of Enzalutamide in Subjects With Advanced Hepatocellular Carcinoma
NCT02528643
  1. San Francisco, California
  2. Skokie, Illinois
  3. Minneapolis, Minnesota
  4. Lebanon, New Hampshire
  5. Portland, Oregon
  6. Philadelphia, Pennsylvania
  7. Philadelphia, Pennsylvania
  8. Milwaukee, Wisconsin
  9. Toronto, Ontario
  10. Montreal, Quebec
  11. Montreal,
  12. Kowloon,
  13. Shatin,
  14. Rozzano, Milan
  15. Benevento,
  16. Milano,
  17. Milan,
  18. Padova,
  19. Pavia,
  20. Seongnam-Si, Gyeonggi-do
  21. Seoul, Seoul Teugbyeolsi
  22. Seoul,
  23. Seoul,
  24. Seoul,
  25. Seoul,
  26. San Juan,
  27. Barcelona,
  28. Cordoba,
  29. Madrid,
  30. Douliu,
  31. Tainan,
  32. Tainan,
  33. Taipei City,
  34. Birmingham,
  35. London,
  36. London,
  37. Manchester,
  38. Wirral,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Study to Assess the Efficacy and Safety of Enzalutamide in Subjects With Advanced Hepatocellular Carcinoma
Official Title  ICMJE A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Enzalutamide in Subjects With Advanced Hepatocellular Carcinoma
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Advanced Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: enzalutamide
    Participants received 160 mg enzalutamide oral capsules (4 x 40 mg capsules) one daily.
    Other Names:
    • MDV3100
    • Xtandi
  • Drug: placebo
    Participants received placebo to match enzalutamide oral capsules once daily.
Study Arms  ICMJE
  • Experimental: Enzalutamide
    Participants received enzalutamide 160 mg once daily until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.
    Intervention: Drug: enzalutamide
  • Placebo Comparator: Placebo
    Participants received placebo once daily until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 15, 2017)
165
Original Estimated Enrollment  ICMJE
 (submitted: August 18, 2015)
144
Estimated Study Completion Date  ICMJE September 2020
Actual Primary Completion Date October 2, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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.

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:

    • 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-? 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Hong Kong,   Italy,   Korea, Republic of,   Puerto Rico,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02528643
Other Study ID Numbers  ICMJE 9785-CL-3021
2014-004283-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials:Study Protocol
Supporting Materials:Statistical Analysis Plan (SAP)
Supporting Materials:Clinical Study Report (CSR)
Time Frame:Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria:Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL:https://www.clinicalstudydatarequest.com/
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director:Executive Medical DirectorAstellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP