Houston, Texas 77030


Purpose:

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.


Study summary:

Study Drug Administration Each study cycle is 28 days. If you are found to be eligible to take part in this study, you will take 4 apalutamide tablets by mouth 1 time at about the same time each day with or without food. You will take 4 abiraterone acetate tablets by mouth 1 time at about the same time every day. Do not eat for at least 2 hours before your dose and for at least 1 hour after the dose of abiraterone acetate. You will take prednisone by mouth 1 time every day. You can take the dose with or without food, but it is recommended that you take prednisone with a meal. You may take these tablets together, when possible. All tablets should be swallowed whole and not crushed or chewed. If you overdose (take 2 days of study drugs or more in 24 hours), contact the study doctor right away. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visit. Study Visits On Day 1 of Week 1: - You will have a physical exam. - You will have an EKG. - Blood (about 3-4 teaspoons) will be drawn for routine testing and to check for genetic mutations (changes). On Day 1 of Week 4 and then every 4 weeks starting at Week 9 (Weeks 13, 17, 21, and so on): - You will have a physical exam - You will have an EKG (Weeks 5 and 9). - Blood (about 3-4 teaspoons) will be drawn for routine testing and to check your PSA levels. During Week 9, this sample will also be used to check your testosterone levels. On Day 1 of Week 13 and every 12 weeks after that (Weeks 25, 37, 49, and so): - You will have an EKG. - Blood (about 3 teaspoons) will be drawn for routine testing. - At Week 13 only, you will have a chest x-ray, MRI, and a bone scan to check the status of the disease. If the chest x-ray shows signs of disease, you will also have a chest CT scan. End-of-Treatment Visit As soon as possible after your last dose of study drugs: - You will have a physical exam. - You will have an EKG. - Blood (about 3-4 teaspoons) will be drawn for routine testing and to check your PSA and testosterone levels. - You will have a CT scan or MRI. Follow-Up Visit Within 30 days after your last dose of study drug: - You will have a physical exam. - You will have an EKG. - Blood (about 3 teaspoons) will be drawn for routine tests.


Criteria:

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.


NCT ID:

NCT03360721


Primary Contact:

Study Chair
Eleni Efstathiou, MD
UT MD Anderson Cancer Center

Eleni Efstathiou, MD
Phone: 713-792-2830
Email: eefstathiou@mdanderson.org


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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