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

NCT01650194

Last updated date
Study Location
Site US2492 MD Anderson Cancer Ctr
Houston, Texas, 77030, 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.
Metastatic Castration-Resistant Prostate Cancer
Sex
Male
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
0 +
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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


- 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

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Advanced Information
Descriptive Information
Brief Title  ICMJE A Study to Determine Safety and Tolerability of Enzalutamide (MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients
Official Title  ICMJE A Phase 2 Study Determining Safety and Tolerability of Enzalutamide (Formerly MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients
Brief Summary 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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Castration-Resistant Prostate Cancer
Intervention  ICMJE
  • Drug: enzalutamide
    Participants received 160 mg of enzalutamide orally once daily (4 capsules, 40 mg each).
    Other Name: MDV3100
  • Drug: abiraterone acetate
    Participants received 1000 mg of abiraterone acetate orally once daily (4 tablets, 250 mg each).
  • Drug: prednisone
    Participants received 5 mg of prednisone orally twice daily (2 tablets, 5 mg each).
Study Arms  ICMJE Experimental: Enzalutamide + Abiraterone + Prednisone
Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.
Interventions:
  • Drug: enzalutamide
  • Drug: abiraterone acetate
  • Drug: prednisone
Publications * 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. Review.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: July 24, 2012)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 4, 2018
Actual Primary Completion Date January 4, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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/?L, platelet count < 75,000/?L, 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-? 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
Sex/Gender  ICMJE
Sexes Eligible for Study:Male
Ages  ICMJE Child, 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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01650194
Other Study ID Numbers  ICMJE 9785-CL-0011
Has Data Monitoring Committee No
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 trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. 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 Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators  ICMJE
Study Director:Associate Medical DirectorAstellas Pharma Global Development
PRS Account Astellas Pharma Inc
Verification Date January 2019

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