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`Trial record 38 of 101 for: abiraterone AND Prednisone
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`Phase II Clinical Trial of Abiraterone Acetate Without Exogenous Glucocorticoids in Men With Castration-
`resistant Prostate Cancer With Correlative Assessment of Hormone Intermediates.
`
`This study is ongoing, but not recruiting participants.
`
`Sponsor:
`Dana-Farber Cancer Institute
`
`Collaborator:
`Janssen Research & Development, LLC
`
`Information provided by (Responsible Party):
`Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
`
`ClinicalTrials.gov Identifier:
`NCT02025010
`
`First received: December 13, 2013
`Last updated: September 12, 2016
`Last verified: September 2016
`History of Changes
`
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`
`No Study Results Posted
`
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`
` Purpose
`
`This study is comparing the safety and effectiveness of abiraterone acetate alone, followed by the addition of prednisone (when the
`participant's disease worsens or the physician feels it would lessen symptoms of toxicity) versus the current approved treatment regimen which
`involves the concomitant use of prednisone in conjunction with abiraterone acetate. Additionally, this study is also examining why participants
`stop responding to treatment with abiraterone acetate by evaluating blood and tissue.
`
`Condition
`
`Intervention
`
`Castration-resistant Prostate Cancer Drug: abiraterone acetate
`Drug: prednisone
`Procedure: pre-treatment and progression tumor biopsies
`Genetic: assessment of serum corticosteroid intermediates and ACTH
`
`Phase
`
`Phase 2
`
`Interventional
`Study Type:
`Study Design: Endpoint Classification: Safety/Efficacy Study
`Intervention Model: Single Group Assignment
`Masking: Open Label
`Primary Purpose: Treatment
`
`Official Title:
`
`Phase II Clinical Trial of Abiraterone Acetate Without Exogenous Glucocorticoids in Men With Castration-resistant Prostate
`Cancer With Correlative Assessment of Hormone Intermediates.
`
`Resource links provided by NLM:
`
`Genetics Home Reference related topics: prostate cancer
`
`MedlinePlus related topics: Biopsy Cancer Health Checkup Hormones Prostate Cancer Steroids
`
`Drug Information available for: Prednisone Abiraterone acetate
`
`U.S. FDA Resources
`
`Further study details as provided by Dana-Farber Cancer Institute:
`
`Primary Outcome Measures:
`
`The proportion of participants requiring the addition of prednisone to manage symptoms of persistent or severe mineralocorticoid excess
`(Hypertension and Hypokalemia). [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
`
`Amerigen Exhibit 1139
`Amerigen v. Janssen IPR2016-00286
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`Secondary Outcome Measures:
`
`Assessment of safety and tolerability associated with AA monotherapy and the addition of prednisone to AA. [ Time Frame: 2 Years ]
`[ Designated as safety issue: Yes ]
`
`The proportion of participants requiring the addition of prednisone to manage symptoms of severe fatigue. [ Time Frame: 2 years ]
`[ Designated as safety issue: No ]
`
`Assessment of changes in serum concentrations of corticosteroid intermediates between baseline and subsequent assessment visits.
`[ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
`
`Assessment of changes in serum concentrations of ACTH between baseline and subsequent assessment visits. [ Time Frame: 2 Years ]
`[ Designated as safety issue: No ]
`
`Assessment of changes in serum concentrations of androgen (including testosterone, DHT and androgen precursors) between baseline and
`subsequent assessment visits. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
`
`Assessment of changes in BMI and hemoglobin-A1c between baseline and subsequent assessment visits. [ Time Frame: 2 Years ]
`[ Designated as safety issue: Yes ]
`
`Assessment of PSA response and duration of PSA response to AA monotherapy. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
`
`Assessment of PSA response and duration of PSA response to addition of prednisone to AA at time of PSA progression on AA
`monotherapy. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
`
`Assessment of the response of measurable disease and time to progression of measurable disease to AA monotherapy. [ Time Frame: 2
`Years ] [ Designated as safety issue: No ]
`
`Assessment of response of measurable disease and time to progression of measurable disease to addition of prednisone to AA at time of
`PSA progression on AA monotherapy. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
`
`60
`Enrollment:
`December 2013
`Study Start Date:
`June 2018
`Estimated Study Completion Date:
`Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
`
`Arms
`
`Assigned Interventions
`
`Experimental: abiraterone acetate
`
`Drug: abiraterone acetate
`
`Pre-treatment and progression tumor biopsies.
`
`Four 250 mg tablets (1,000 mg) of abiraterone acetate
`(AA) taken orally on 28 day cycles.
`
`For participants who experience symptoms of persistent or
`severe hypertension or hypokalemia, prednisone 5 mg by
`mouth twice daily.
`
`For participations who tolerate AA monotherapy without the
`addition of prednisone to manage symptoms of persistent
`or severe mineralocorticoid excess, prednisone 5 mg by
`mouth twice daily will be added at PSA progression.
`
`Participants will undergo assessment of serum
`corticosteroid intermediates and ACTH at baseline and
`subsequent treatment visits for correlation with symptoms
`of mineralocorticoid excess.
`
`Daily four 250 mg tablets (1,000 mg) of AA taken orally for 28 day cycles.
`No food should be consumed for at least two hours before the dose and for
`at least one hour after the dose. The tablets should be swallowed whole
`with water. Tablets should not be crushed or chewed.
`
`Other Name: JNJ21208
`Drug: prednisone
`
`Take with food 5 mg Oral Twice daily
`
`Other Name: exogenous glucocorticoids
`Procedure: pre-treatment and progression tumor biopsies
`
`Participants will undergo pre-treatment and progression tumor biopsies.
`After the progression biopsy is performed, protocol therapy will be
`discontinued. Participants who stop protocol therapy before receiving four
`cycles of AA will not be asked to undergo the second biopsy.
`Genetic: assessment of serum corticosteroid intermediates and ACTH
`
`•Participants will undergo assessment of serum corticosteroid
`intermediates and ACTH at baseline and subsequent treatment visits for
`correlation with symptoms of mineralocorticoid excess.
`
`Detailed Description:
`
`Participants will be treated with abiraterone acetate (AA) in 28-day cycles. Participants will be monitored (weekly for the first two cycles, then
`on Day 1 of each subsequent cycle) for symptoms of persistent or severe mineralocorticoid excess (including hypertension, hypokalemia).
`For participants who experience symptoms of persistent or severe hypertension or hypokalemia as detailed in the above schema,
`prednisone 5 mg by mouth twice daily will be added. We will monitor for other symptoms of AA toxicity to include fluid retention and fatigue.
`
`For participations who tolerate AA monotherapy without the addition of prednisone to manage symptoms of persistent or severe
`mineralocorticoid excess, prednisone 5 mg by mouth twice daily will be added at Prostate Specific Antigen (PSA) progression. Participants
`will be continued on study until symptomatic or radiographic progression or taken off study for another reason as detailed in protocol.
`
`Participants will undergo pre-treatment and progression tumor biopsies. Participants will also undergo pre-treatment and progression tumor
`biopsies for assessment of possible mechanisms of AA resistance. After the progression biopsy is performed, protocol therapy will be
`discontinued. Participants who stop protocol therapy before receiving four cycles of AA will not be asked to undergo the second biopsy.
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`Correlative Studies: Participants will undergo assessment of serum corticosteroid intermediates and Adrenocorticotropic hormone (ACTH) at
`baseline and subsequent treatment visits for correlation with symptoms of mineralocorticoid excess.
`
` Eligibility
`
`18 Years and older (Adult, Senior)
`Ages Eligible for Study:
`Genders Eligible for Study: Male
`Accepts Healthy Volunteers: No
`
`Criteria
`
`Inclusion Criteria:
`
`Participants must meet the following criteria on screening examination to be eligible to participate in the study:
`
`Be a male ≥ 18 years of age.
`
`Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate without >50% neuroendocrine differentiation
`or small cell histology.
`
`Participants must have progressive disease as defined by one or more of the following:
`
`Castrate resistant disease as defined by Prostate cancer working Group (PCWG).[30] Participants must have a rise in PSA on two
`successive determinations at least one week apart and PSA levels ≥ 2 ng/ml (only the screening PSA needs to be ≥ 2 ng/ml) and
`testosterone levels < 50 ng/dL.
`
`Soft tissue progression defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
`
`Bone disease progression defined by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) with two or more new lesions on bone scan.
`[30]
`
`Castration-resistant prostate cancer (CRPC) with metastatic disease with at least one site of metastatic disease must be amenable to needle
`biopsy. Soft tissue biopsy sites include: lymph node or visceral metastases. Bone sites include lumbar vertebrae, pelvic bones and long
`bones. Excluded sites are thoracic, cervical vertebrae, skull and rib lesions. Biopsy site will be selected with guidance of interventional
`radiologist determining best site to optimize balance of obtaining useful tissue for analysis and minimizing risk.
`
`Participants without orchiectomy must be maintained on Luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy.
`
`Participants may have had any number of previous hormonal therapies (antiandrogens including enzalutamide, steroids, estrogens,
`finasteride, dutasteride, ketoconazole) provided these were discontinued ≥ 4 weeks before starting the trial.
`
`Participants may have had up to two previous cytotoxic therapeutic regimens provided these were discontinued ≥ 4 weeks before starting
`the trial.
`
`At least a 4 week interval from previous prostate cancer treatment other than LHRH agonist/antagonist therapy or bisphosphonates to the
`start of protocol therapy.
`
`Participants receiving bisphosphonates therapy can be maintained on this therapy. If participants have not started bisphosphonates, it is
`recommended that they start treatment after the first biopsy.
`
`Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky >60%, see Appendix A).
`
`Participants must have normal organ and marrow function as defined below:
`
`Platelets > 50,000/microliter (mcL)
`
`Serum potassium ≥ 3.5 mmol/L (independent of potassium supplementation)
`
`Serum albumin ≥ 3.0 g/dL
`
`Aspartate transaminase (AST), Alanine transaminase (ALT), and total bilirubin ≤ 1.5 x Institutional Upper Limit of Normal (ULN).
`
`Partial thromboplastin time (PTT) ≤ 60, International Normalized Ratio (INR) ≤ 1.5 Institutional ULN unless on warfarin therapy (investigator
`would need to determine if safe for participant to stop warfarin prior to biopsy)
`
`Controlled blood pressure (systolic blood pressure < 140 and diastolic blood pressure <90) on no more than three anti-hypertensive agents.
`Drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each
`formulation.
`
`EKG showing a normal QTc interval (QTc < 450 msec).
`
`Left ventricular ejection fraction ≥ 50%.
`
`Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study
`and are willing to participate in the study.
`
`Be willing/able to adhere to the prohibitions and restrictions specified in this protocol.
`
`Written Authorization for Use and Release of Health and Research Study Information (US sites only) has been obtained.
`
`Able to swallow the study drug whole as a tablet.
`
`Willing to take AA on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose AA
`is taken.
`
`Participants who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as
`determined to be acceptable by the PI during the treatment period and for 1 week after last dose of AA.
`
`Exclusion Criteria:
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`Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
`
`Uncontrolled illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris,
`cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or would make
`prednisone/prednisolone (corticosteroid) use contraindicated.
`
`Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or
`unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at
`baseline.
`
`Thromboembolism within 6 months of Cycle 1, Day 1.
`
`Severe hepatic impairment (Child-Pugh Class C).
`
`History of pituitary or adrenal dysfunction.
`
`Poorly controlled diabetes.
`
`History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
`
`Have a pre-existing condition that warrants long-term corticosteroid use.
`
`Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other
`malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for
`recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years:
`superficial bladder cancer, basal cell or squamous cell carcinoma of the skin.
`
`Known brain metastasis.
`
`Prior therapy with AA.
`
`Have known allergies, hypersensitivity, or intolerance to AA or prednisone or their excipients.
`
`Surgery or local prostatic intervention within 30 days of the first dose. In addition, any clinically relevant issues from the surgery must have
`resolved prior to Cycle 1, Day 1.
`
`Major surgery or radiation therapy within 4 weeks of Cycle 1, Day 1.
`
`Strontium-89 or samarium-153 therapy within 4 weeks of Cycle 1, Day 1.
`
`Radiotherapy, chemotherapy or immunotherapy within 4 weeks, or single fraction of palliative radiotherapy within 14 days of administration
`of Cycle 1, Day 1.
`
`Current enrollment in an investigational drug or device study or participation in such a study within 30 days of Cycle 1, Day 1.
`
`Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a NCI Common Toxicity Criteria for Adverse
`Effects (CTCAE) version 4 grade of ≤ 1. Chemotherapy induced alopecia and grade 2 peripheral neuropathy are allowed.
`
`Condition or situation which, in the investigator's opinion, may put the participant at significant risk, may confound the study results, or may
`interfere significantly with participant's participation in the study.
`
`Individuals not willing to comply with the procedural requirements of this protocol.
`
`HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AA.
`
` Contacts and Locations
`
`Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a
`study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general
`information, see Learn About Clinical Studies.
`
`Please refer to this study by its ClinicalTrials.gov identifier: NCT02025010
`
`Locations
`
`United States, Massachusetts
`
`Brigham and Women's Hospital
`Boston, Massachusetts, United States, 02115
`
`Dana-Farber Cancer Institute
`Boston, Massachusetts, United States, 02115
`
`United States, New York
`
`Memorial Sloan Kettering Cancer Center Basking Ridge
`Basking Ridge, New York, United States, 07920
`
`Memorial Sloan Kettering Cancer Center Commack
`Commack, New York, United States, 11725
`
`Memorial Sloan-Kettering Cancer Center
`New York, New York, United States, 10065
`
`Memorial Sloan Kettering Cancer Center Rockville Centre
`
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`Rockville Centre, New York, United States, 11510
`
`Memorial Sloan Kettering Cancer Center Sleepy Hollow
`Sleepy Hollow, New York, United States, 10591
`
`Memorial Sloan Kettering Cancer Center West Harrison
`West Harrison, New York, United States, 10604
`
`Sponsors and Collaborators
`
`Dana-Farber Cancer Institute
`
`Janssen Research & Development, LLC
`
`Investigators
`
`Principal Investigator: Mary-Ellen Taplin, MD Dana-Farber Cancer Institute
`
` More Information
`
`Mary-Ellen Taplin, MD, Principal Investigators, Dana-Farber Cancer Institute
`Responsible Party:
`ClinicalTrials.gov Identifier: NCT02025010 History of Changes
`Other Study ID Numbers:
`13-449
`Study First Received:
`December 13, 2013
`Last Updated:
`September 12, 2016
`Health Authority:
`United States: Institutional Review Board
`
`Keywords provided by Dana-Farber Cancer Institute:
`castration-resistant prostate cancer
`
`Additional relevant MeSH terms:
`Prednisone
`Abiraterone Acetate
`Prostatic Neoplasms
`Genital Neoplasms, Male
`Urogenital Neoplasms
`Neoplasms by Site
`Neoplasms
`Genital Diseases, Male
`Prostatic Diseases
`Hormones
`Glucocorticoids
`
`ClinicalTrials.gov processed this record on September 27, 2016
`
`Mineralocorticoids
`Hormones, Hormone Substitutes, and Hormone Antagonists
`Physiological Effects of Drugs
`Anti-Inflammatory Agents
`Antineoplastic Agents, Hormonal
`Antineoplastic Agents
`Steroid Synthesis Inhibitors
`Enzyme Inhibitors
`Molecular Mechanisms of Pharmacological Action
`Hormone Antagonists
`Cytochrome P-450 Enzyme Inhibitors
`
`5
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