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Metastatic Castration-Resistant Prostate CancerPhase 2NCT01650194

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

A Phase 2 study testing enzalutamide, abiraterone acetate and prednisone in people with Metastatic Castration-Resistant Prostate Cancer, run by Astellas Pharma Global Development, Inc. at 1 site in United States.

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 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… Read more about this study

Who is it for?
Any age, men only
What is being tested?
enzalutamide, abiraterone acetate and prednisone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited States
Study dates
9 Jul 2012to 4 Jan 2018
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 Any age
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 25Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Site US2492 MD Anderson Cancer Ctr

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: 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

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.

Read the 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.

Being tested
enzalutamide, abiraterone acetate, prednisone
Keywords
abiraterone acetate, prednisone, enzalutamide, cancer, prostate, MDV3100
Medical subject headings
Neoplasms

What participants receive

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

  • enzalutamideDrug

    Also called MDV3100

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

  • abiraterone acetateDrug

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

  • prednisoneDrug

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

Study groups in NCT01650194
Study groupRoleWhat they receive
Enzalutamide + Abiraterone + PrednisoneExperimentalParticipants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.
Receives: Drug: enzalutamide; Drug: abiraterone acetate; Drug: prednisone

What is being measured

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

  1. Number of Participants With Adverse Events (AEs)

    A treatment-emergent adverse event (TEAE) was defined as an adverse event occurring or worsening between the start of study treatment date and the latest date of 30 days after the last dose date or the 30-day follow-up visit date, and not later than the data cut-off date or the date of death. AEs, including abnormal clinical laboratory values, were graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) guidelines (V4.03).

    Measured: From the first dose of study drug administration up 30 days following the last dose of study drug date, with a median duration of treatment of 10.1 months.

Secondary outcomes (18)

  1. Change From Baseline in Testosterone Concentration in Bone Marrow Aspirate

    Testosterone concentration in bone marrow aspirate was measured by laboratory results derived from bone marrow samples processed through liquid chromatography mass spectrometry.

    Measured: Baseline and Week 9

  2. Change From Baseline in Dihydrotestosterone (DHT) Concentration in Bone Marrow Aspirate

    DHT concentration in bone marrow aspirate was to be measured by laboratory results derived from bone marrow samples processed through liquid chromatography mass spectrometry. DHT bone data were not collected.

    Measured: Baseline and Week 9

  3. Change From Baseline in Cortisol in Bone Marrow Aspirate

    Cortisol in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

    Measured: Baseline and Week 9

  4. Change From Baseline in Androstenedione in Bone Marrow Aspirate

    Androstenedione in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

    Measured: Baseline and Week 9

  5. Change From Baseline in Progesterone in Bone Marrow Aspirate

    Progesterone in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

    Measured: Baseline and Week 9

  6. Change From Baseline in Pregnenolone in Bone Marrow Aspirate

    Pregnenolone in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

    Measured: Baseline and Week 9

  7. Change From Baseline in Testosterone Concentration in Blood

    Testosterone concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

    Measured: Baseline and Week 9

  8. Change From Baseline in DHT Concentration in Blood

    DHT concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry. The endpoint could not be analyzed since no participants had DHT levels over the lower limit of quantification (LLOQ).

    Measured: Baseline and Week 9

  9. Change From Baseline in Cortisol Concentration in Blood

    Cortisol concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

    Measured: Baseline and Week 9

  10. Change From Baseline in Androstenedione Concentration in Blood

    Androstenedione concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

    Measured: Baseline and Week 9

  11. Change From Baseline in Progesterone Concentration in Blood

    Progesterone concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

    Measured: Baseline and Week 9

  12. Change From Baseline in Pregnenolone Concentration in Blood

    Pregnenolone concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

    Measured: Baseline and Week 9

  13. Change From Baseline to End-of-Treatment (EoT) in Prostate-Specific Antigen (PSA) Levels

    Prostate-specific antigen progression by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) was defined as a PSA increase ≥25% and ≥2 ng/ml above the post-baseline nadir, and which was confirmed by the first subsequent value of 3 or more weeks later.

    Measured: Baseline and EoT; the median duration of treatment was 10.1 months.

  14. Progression Free Survival (PFS)

    PFS was measured as the time from the date of first dose of any drug of the study combination treatment until the first evidence of documented progression (a composite endpoint consisting of radiographic progression or PSA progression by PCWG2 or clinical deterioration) or death in the absence of progression (whichever came first) or the date last known to be progression free. The Kaplan-Meier (KM) 95% CI was based on Brookmeyer and Crowley robust non-parametric method.

    Measured: Up to 1849 days

  15. Percentage of Participants With Objective Response for Soft Tissue Lesions According to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST)

    Objective response was based on RECIST version 1.1 for soft tissue lesion on Magnetic resonance imaging (MRI) / Computerized tomography (CT) and the PCWG2 guidelines for bone lesions on bone scans and was defined as partial response (PR) or complete response (CR) based on the investigators' assessments of target, non-target and new lesions while on study treatment. The 95% for objective response rate was based on exact binomial 95% confidence interval (Clopper-Pearson).

    Measured: Up to 1849 days

  16. Bone Scan Response at EoT

    PD: ≥1 of 3 criteria: PSA progression: ≥2 rising PSA levels, interval of ≥1 week between each determination. Soft tissue disease progression: RECIST 1.1. Bone disease progression: PCWG2 criteria (≥2 or new lesions on bone scan compared with prior scan). Target lesion CR: disappearance of all target lesions, PR as ≥30% decrease in sum of longest diameter (LD) of target lesions, referencing baseline sum LD, SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing smallest sum LD since treatment start, PD ≥20% increase in sum of LD of target lesions, referencing smallest sum LD recorded since treatment start or appearance of ≥1 new lesions. Non-target lesions CR: disappearance of all non-target lesions and normalization of tumor marker level, SD: persistence of ≥1 non-target lesions and/or maintenance of tumor marker level above normal limits, PD: appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions.

    Measured: EoT; the median duration of treatment was 10.1 months.

  17. Change From Baseline to EoT in Bone Specific Alkaline Phosphatase

    Bone metabolism marker bone specific alkaline phosphatase levels were derived from blood samples collected.

    Measured: Baseline and EoT; the median duration of treatment was 10.1 months.

  18. Change From Baseline in Urine N-Telopeptide

    Bone metabolism marker urine N-telopeptide levels were derived from urine samples collected.

    Measured: Baseline and Week 9

Timeline

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

  1. First posted26 Jul 2012 (estimated)
  2. Study start9 Jul 2012
  3. Primary completion4 Jan 2018
  4. Study completion4 Jan 2018

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01650194
Sponsor's protocol ID
9785-CL-0011
Status last verified
Nov 2024
First submitted
24 Jul 2012
Last updated
10 Dec 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

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. doi: 10.2174/1389450116666150907101044.

    PubMed 26343110

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing enzalutamide, abiraterone acetate and prednisone in people with Metastatic Castration-Resistant Prostate Cancer, run by Astellas Pharma Global Development, Inc. at 1 site in United States.

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 12 inclusion and 25 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 10 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 1 site in United States. 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. 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 5 Feb 2019). 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?

Number of Participants With Adverse Events (AEs) (time frame: From the first dose of study drug administration up 30 days following the last dose of study drug date, with a median duration of treatment of 10.1 months.). 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 NCT01650194, 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 10 Dec 2024.

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