A Study to Determine Safety and Tolerability of Enzalutamide (MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients

NCT ID: NCT01650194

Last Updated: 2024-12-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-07-09

Study Completion Date

2018-01-04

Brief Summary

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The purpose of this study was to explore the safety and tolerability of enzalutamide in combination with abiraterone acetate plus prednisone. Subjects diagnosed with cancer of the prostate that was getting worse and spreading to the bone despite receiving hormone treatment were enrolled and received study treatment until disease progression.

Detailed Description

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For the study duration, all subjects maintained androgen deprivation with a gonadotropin releasing hormone (GnRH) agonist or antagonist or orchiectomy. Study drug was administered until disease progression. Disease progression was defined as a composite endpoint consisting of either clinical deterioration, radiographic progression or prostate-specific antigen (PSA) progression according to the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria.

Conditions

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Metastatic Castration-Resistant Prostate Cancer

Keywords

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abiraterone acetate prednisone enzalutamide cancer prostate MDV3100

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Enzalutamide + Abiraterone + Prednisone

Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.

Group Type EXPERIMENTAL

enzalutamide

Intervention Type DRUG

Participants received 160 mg of enzalutamide orally once daily (4 capsules, 40 mg each).

abiraterone acetate

Intervention Type DRUG

Participants received 1000 mg of abiraterone acetate orally once daily (4 tablets, 250 mg each).

prednisone

Intervention Type DRUG

Participants received 5 mg of prednisone orally twice daily (2 tablets, 5 mg each).

Interventions

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enzalutamide

Participants received 160 mg of enzalutamide orally once daily (4 capsules, 40 mg each).

Intervention Type DRUG

abiraterone acetate

Participants received 1000 mg of abiraterone acetate orally once daily (4 tablets, 250 mg each).

Intervention Type DRUG

prednisone

Participants received 5 mg of prednisone orally twice daily (2 tablets, 5 mg each).

Intervention Type DRUG

Other Intervention Names

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MDV3100

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
* Presence of metastatic disease to the bone
* Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
* Subject receiving bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to Day 1
* Progressive disease defined as one or more of the following three criteria (Note: subjects who received an antiandrogen must demonstrate disease progression following discontinuation of antiandrogen):

* PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥ 2 ng/mL
* Soft tissue disease progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
* Bone disease progression defined by PCWG2 criteria (two or more new lesions on bone scan compared with prior scan)
* Subject previously treated with chemotherapy must have no more than two prior chemotherapy regimens for the treatment of metastatic prostate cancer
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Agree to use a double-barrier method of contraception which involves the use of a condom in combination with one of the following: contraceptive sponge, diaphragm, or cervical ring with spermicidal gel or foam, if having sex with a woman of child-bearing potential during the length of the study and for one week after abiraterone is discontinued and for at least three months after enzalutamide is discontinued
* Subject agrees not to participate in another interventional study while on treatment

Exclusion Criteria

* Known or suspected metastases in the brain
* Absolute neutrophil count \< 1,000/μL, platelet count \< 75,000/μL, and hemoglobin \< 9 g/dL (NOTE: subject may not have received any growth factors or blood transfusions within seven days of the hematologic laboratory values obtained at the Screening visit)
* Total bilirubin (TBL), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal
* Creatinine (Cr) \> 2 mg/dL
* Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5-α reductase inhibitors (finasteride, dutasteride), estrogens, chemotherapy, or biologic therapy within 4 weeks of Day 1 visit
* Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) of Day 1 visit, or radionuclide therapy within 8 weeks of Day 1
* Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
* Structurally unstable bone lesions suggesting impending fracture
* History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit)
* Clinically significant cardiovascular disease including:

* Myocardial infarction within 6 months of Screening visit;
* Uncontrolled angina within 3 months of Screening visit;
* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the Screening visit results in a left ventricular ejection fraction that is ≥ 45%
* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
* Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the Electrocardiogram (ECG) \> 470 msec.
* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
* Hypotension (systolic blood pressure \< 86 mmHg or bradycardia with a heart rate of \<50 beats per minute on the ECG., unless pharmaceutically induced and thus reversible (i.e. beta blockers).
* Uncontrolled hypertension as indicated by a resting systolic blood pressure \>170 mmHg or diastolic blood pressure \>105 mmHg
* Prior use of ketoconazole, abiraterone acetate or enzalutamide, or participation in a previous clinical trial of ketoconazole, abiraterone acetate or enzalutamide
* History of significant bleeding disorder unrelated to cancer, including:

* Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) of Screening visit
* History of GI bleeding within 6 months of Screening visit
* Active or symptomatic viral hepatitis or chronic liver disease
* Known history of pituitary or adrenal dysfunction
Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

INDUSTRY

Sponsor Role collaborator

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Associate Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development

Locations

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Site US2492 MD Anderson Cancer Ctr

Houston, Texas, United States

Site Status

Countries

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United States

References

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Assi R, Temraz S, Shamseddine A, Mukherji D. New Compounds Targeting the Androgen Receptor for Treatment of Advanced Prostate Cancer. Curr Drug Targets. 2016;17(3):290-302. doi: 10.2174/1389450116666150907101044.

Reference Type DERIVED
PMID: 26343110 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://astellasclinicalstudyresults.com/study.aspx?ID=300

Link to results on the Astellas Clinical Study Results website

Other Identifiers

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9785-CL-0011

Identifier Type: -

Identifier Source: org_study_id