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Apalutamide, Abiraterone Acetate, and Prednisone in Treating Participants With Metastatic Castration Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03360721
Recruitment Status : Recruiting
First Posted : December 4, 2017
Last Update Posted : May 15, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well apalutamide and abiraterone acetate work in treating participants with castration resistant prostate cancer that has spread to other places in the body. Abiraterone acetate and apalutamide may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunosuppressive therapy, such as prednisone, is used to decrease the body's immune response and may improve bone marrow function. Giving apalutamide, abiraterone acetate, and prednisone may work better in treating participants with castration resistant prostate cancer.

Condition or disease Intervention/treatment Phase
Castration-Resistant Prostate Carcinoma Prostate Adenocarcinoma Without Neuroendocrine Differentiation Stage IV Prostate Cancer AJCC v8 Stage IVA Prostate Cancer AJCC v8 Stage IVB Prostate Cancer AJCC v8 Drug: Abiraterone Acetate Drug: Apalutamide Drug: Prednisone Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To assess the radiographic progression free survival (PFS) of men with metastatic castration resistant prostate cancer (mCRPC) who are selected for treatment based on positive biomarker signature.

SECONDARY OBJECTIVES:

I. Safety. II. Composite progression free survival (PFSc) defined by Prostate Cancer Working Group 2 (PCWG2) (radiographic progression, prostate specific antigen [PSA] progression, or clinical deterioration).

III. Overall survival. IV. Exploratory biomarker analyses. V. Measures of prostate specific antigen (PSA) decline and associations with outcome.

VI. Radiologic response by PCWG2 criteria. VII. Measures of circulating tumor cell (CTC) and conversion to undetectable and/or favorable < 5.

OUTLINE:

Participants receive abiraterone acetate orally (PO) once daily (QD), apalutamide PO QD, and prednisone PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up for up to 16 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Study of Apalutamide and Abiraterone Acetate in Castration-Resistant Metastatic Prostate Cancer Patients Evaluating a Predetermined Biomarker Signature
Actual Study Start Date : March 6, 2018
Estimated Primary Completion Date : October 31, 2020
Estimated Study Completion Date : October 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (abiraterone acetate, apalutamide, prednisone)
Participants receive abiraterone acetate PO once daily QD, apalutamide PO QD, and prednisone PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Yonsa
  • Zytiga

Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • Erleada
  • JNJ 56021927
  • JNJ-56021927

Drug: Prednisone
Given PO
Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Up to 3 years ]
    PFS is defined as the time from enrollment until radiographic progression (event), death from any cause (event), start of other therapy (censor) or last follow-up without progression (censor), whichever comes first.


Secondary Outcome Measures :
  1. Summary of Most Common Adverse Events [ Time Frame: Up to 3 years ]
    Adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with grade and attribution to study drug

  2. Composite progression free survival (PFSc) [ Time Frame: Up to 3 years ]
    Composite progression free survival (PFSc) is defined as the time from protocol treatment start until PCWG2 progression (radiographic progression, PSA Progression, or clinical deterioration - event), death (event), starting new treatment (censor) or last follow-up without PCWG2 progression (censor), whichever comes first.

  3. Overall Survival (OS) [ Time Frame: Up to 3 years ]
    Overall Survival is the time from protocol treatment start until death (event) or last contact (censor)

  4. Biomarkers: androgen expression signaling and survival escape pathway signaling [ Time Frame: Up to 3 years ]
    Marker Evaluable Set (MES) where the MES will consist of all patients with baseline and Week 9 laboratory results derived from bone marrow samples. The number of patients with evaluable results may differ for each laboratory parameter. The MES will be used to assess the effect of treatment with apalutamide on androgen signaling and expression of survival/escape pathways in the bone marrow.

  5. Primary Analysis Set (PAS) [ Time Frame: Up to 3 years ]
    The PAS will consist of all patients who received at least one dose of any drug of the study combination treatment. This set will be used for all survival endpoints as well as safety. PSA will be measured at each time point according to the assessment schedule.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
  • Presence of metastatic disease that can be biopsied by any methodology applicable
  • Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
  • Serum testosterone level =< 50 ng/dL at the screening visit
  • Patients receiving bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to screening
  • Progressive disease defined as one or more of the following three criteria (NOTE: Patients 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 weeks 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)
    • Bone disease progression defined by two or more new lesions on bone scan
  • Patients 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 0-1
  • Serum albumin >= 3.0 g/dL
  • Serum potassium >= 3.5 mmol/L
  • Estimated life expectancy of >= 6 months
  • Able to swallow the study drug and comply with study requirements
  • Willing and able to give informed consent
  • Tumor specimen obtained prior to treatment initiation by interventional radiology guided biopsy will be interrogated per immunohistochemistry (IHC) and features should be as follows for a patient to be eligible

    • Overexpression of androgen receptor (AR)-C terminal and AR-N terminal and PTEN with lack of ARV7 expression along with and ki67 =<10%
    • No RB loss or p53 mutation and
    • No expression of neuroendocrine markers CD56 and chromogranin (all markers assessed by standardized IHC protocols)
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug

    • The methods must consist of a condom and the use of another barrier method (such as a diaphragm or cervical/vault caps) with a spermicidal agent. Your female partner can choose to use an intrauterine device or system (intrauterine device [IUD] or intrauterine system [IUS]) or use birth control pills, injections, or implants instead of a barrier method

Exclusion Criteria:

  • Known allergy to the study drugs or any of its components
  • Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
  • Metastases in the brain
  • Absolute neutrophil count < 1000/uL at the screening visit
  • Platelet count =< 100,000 x 10^9/uL at the screening visit
  • Hemoglobin < 9 g/dL at the screening visit at the screening visit
  • NOTE: patients 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 (Tbili) > 1.5 times the upper limit of normal at the screening visit
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal at the screening visit
  • Creatinine (Cr) > 2 mg/dL at the screening visit
  • History of another malignancy within the previous 2 years with > 30 % probability of relapse other than curatively treated non-melanomatous skin cancer
  • Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5-alpha reductase inhibitors (finasteride, dutasteride), estrogens, chemotherapy, or biologic therapy within 4 weeks of enrollment (day 1 visit)
  • Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) of enrollment (day 1 visit)
  • 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 increase the patient's seizure risk. Also, history of loss of consciousness or transient ischemic attack within 12 months of day 1
  • Clinically significant cardiovascular disease including:

    • Myocardial infarction within 6 months
    • Uncontrolled angina within 6 months
    • Congestive heart failure New York Heart Association (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 results in a left ventricular ejection fraction that is >= 45%
    • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
    • Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening 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 millimeters of mercury or bradycardia with a heart rate of < 50 beats per minute on any ECG taken at the screening visit
    • Bradycardia with a heat rate of < 50 beats per minutes in the screening ECG, unless pharmaceutically induced and reversible
    • Chronically uncontrolled hypertension as indicated by consistently elevated resting blood pressure (systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg) during screening
  • Have used or plan to use from 30 days prior to enrollment (day 1 visit) through the end of the study the following medications known to lower the seizure threshold:

    • Aminophylline/theophylline
    • Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone)
    • Bupropion
    • Insulin
    • Lithium
    • Pethidine
    • Phenothiazine antipsychotics (e.g., prochlorperazine [compazine], chlorpromazine, mesoridazine, thioridazine)
    • Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
  • Prior use of ketoconazloe, enzalutamide, abiraterone or apalutamide or participation in a previous clinical trial of ketoconazloe,enzalutamide, abiraterone or apalutamide
  • Use of an investigational agent within 4 weeks of enrollment (day 1)
  • Gastrointestinal disorder affecting absorption (e.g., gastrectomy)
  • Major surgery within 4 weeks prior to enrollment (day 1)
  • 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)
    • History of gastrointestinal (GI) bleeding within one year
  • Known active or symptomatic viral hepatitis or chronic liver disease
  • Known history of pituitary or adrenal dysfunction
  • Baseline moderate and severe hepatic impairment (Child Pugh class B & C)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03360721


Contacts
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Contact: Eleni Efstathiou, MD 713-792-2830 eefstathiou@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Eleni Efstathiou    713-563-0894    eefstathiou@mdanderson.org   
Principal Investigator: Eleni Efstathiou         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Eleni Efstathiou M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03360721    
Other Study ID Numbers: 2017-0060
NCI-2018-01054 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0060 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: December 4, 2017    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Cortisone
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors