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Study of Apalutamide and Abiraterone Acetate in Castration-Resistant Bone Metastatic Prostate Cancer Patients

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. Identifier: NCT03360721
Recruitment Status : Recruiting
First Posted : December 4, 2017
Last Update Posted : June 4, 2019
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if apalutamide in combination with abiraterone acetate and prednisone can help to control metastatic (has spread) castration-resistant prostate cancer (mCRPC) that has a certain type of biomarker in the tumor. Biomarkers are found in the blood/tissue and may be related to your reaction to the study drug(s).

This is an investigational study. Apalutamide is not FDA approved or commercially available. It is currently being used for research purposes. The combination of abiraterone acetate and prednisone is FDA approved and commercially available for the treatment of mCRPC.

The study doctor can explain how the study drugs are designed to work.

Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.

Condition or disease Intervention/treatment Phase
Castration-resistant Prostate Cancer Metastatic Castration Resistant Prostate Cancer Drug: Abiraterone Acetate 250 MG Oral Tablet [Zytiga] Drug: Apalutamide Drug: Prednisone Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
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 Bone Metastatic Prostate Cancer Patients Evaluating a Predetermined Biomarker Signature
Actual Study Start Date : March 6, 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Abiraterone Acetate + Apalutamide
Abiraterone acetate 1,000 mg (4 x 250 mg tablets each) orally, Apalutamide 240 mg (4 x 60 mg tablets) orally and Prednisone 5 mg orally, all daily for four week course.
Drug: Abiraterone Acetate 250 MG Oral Tablet [Zytiga]
1,000 mg (4 x 250 mg tablets each) orally each day on empty stomach. Treatment with Abiraterone continues through duration of participation.
Other Name: Zytiga

Drug: Apalutamide
240 mg (4 x 60 mg tablets) orally each day with or without food. Apalutamide should be taken as close to the same time each day as possible.
Other Name: ARN-509

Drug: Prednisone
5-mg oral, once daily (recommended to be taken with food). Treatment with prednisone will continue throughout the duration of participation.

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

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, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
  2. Presence of metastatic disease that can be biopsied by any methodology applicable
  3. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration);
  4. Serum testosterone level </= 50 ng/dL at the Screening visit;
  5. Patients receiving bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to screening
  6. 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.
  7. Patients previously treated with chemotherapy must have no more than two prior chemotherapy regimens for the treatment of metastatic prostate cancer;
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
  9. Serum Albumin >/= 3.0 g/dL
  10. Serum potassium >/= 3.5 mmol/L
  11. Estimated life expectancy of >/= 6 months;
  12. Able to swallow the study drug and comply with study requirements;
  13. Willing and able to give informed consent.
  14. Tumor specimen obtained prior to treatment initiation by interventional radiology guided biopsy will be interrogated per IHC and features should be as follows for a patient to be eligible. - overexpression of 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)
  15. 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.

Exclusion Criteria:

  1. Known allergy to the study drugs or any of its components.
  2. 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.
  3. Metastases in the brain;
  4. Absolute neutrophil count < 1000/µL, platelet count </= 100,000 x 10^9/µL, and hemoglobin < 9 g/dL 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);
  5. Total bilirubin (Tbili), >1.5 times the upper limit of normal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal at the Screening visit;
  6. Creatinine (Cr) > 2 mg/dL at the Screening visit;
  7. History of another malignancy within the previous 2 years with >30 % probability of relapse other than curatively treated non-melanomatous skin cancer;
  8. 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)
  9. Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) of enrollment (Day 1 visit);
  10. Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery;
  11. Structurally unstable bone lesions suggesting impending fracture;
  12. 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;
  13. 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);
  14. Continued from 13) 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; - Uncontrolled hypertension as indicated by a resting systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg at the Screening visit.
  15. 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).
  16. Prior use of ketoconazole, enzalutamide, abiraterone or apalutamide or participation in a previous clinical trial of ketoconazole, enzalutamide, abiraterone or apalutamide.
  17. Use of an investigational agent within 4 weeks of enrollment (Day 1)
  18. Gastrointestinal disorder affecting absorption (e.g., gastrectomy)
  19. Major surgery within 4 weeks prior to enrollment (Day 1);
  20. 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 GI bleeding within one year.
  21. Active or symptomatic viral hepatitis or chronic liver disease
  22. Known history of pituitary or adrenal dysfunction
  23. Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)
  24. Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency.
  25. Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate.

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 identifier (NCT number): NCT03360721

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Contact: Eleni Efstathiou, MD 713-792-2830

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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Janssen Scientific Affairs, LLC
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Study Chair: Eleni Efstathiou, MD UT MD Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT03360721     History of Changes
Other Study ID Numbers: 2017-0060
NCI-2018-01054 ( Registry Identifier: NCI CTRP )
First Posted: December 4, 2017    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
metastatic castration resistant prostate cancer
nonsteroidal antiandrogen
androgen signaling

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Abiraterone Acetate
Anti-Inflammatory Agents
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