A Drug-Drug Interaction, Safety and Efficacy Study With JNJ-56021927 (ARN-509) and Abiraterone Acetate in Subjects With Metastatic Castration-Resistant Prostate Cancer

Completed

• Conditions: prostate cancer; 10036958

• Registration Number: NL-OMON44408
• Lead Sponsor: Johnson & Johnson Pharmaceutical

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1. Men >= 18 years of age or older (inclusive).;2. Eastern Cooperative Oncology Group (ECOG) performance status <=2;3. Histologically or cytologically confirmed adenocarcinoma of the prostate.;4. Metastatic disease documented by positive bone scan, or visceral metastasis, or lymph;node disease documented on CT or MRI scans;5. Prostate cancer progression documented by PSA progression according to;PCWG2 or by appearance of new bone lesions on radionuclide bone scan;according to PCWG2 or by radiographic progression according to mRECIST 1.1;6. Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 1.7 nM). If;the subject is being treated with GnRH analogs (subject who has not undergone bilateral;orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study;7. Resolved any acute toxicity to Grade <=1 (except alopecia or Grade <= 2 neuropathy) due;to prior chemotherapy or radiotherapy;8. Bone sparing therapies (eg, bisphosphonates, denosumab) usage is allowed if subjects;are on a stable dose for at least 4 weeks prior to Cycle 1, Day 1;9. Adequate bone marrow and organ function defined as: Hemoglobin >=9.0 g/dL, independent of transfusion and/or growth factor support; ANC count >=1,500 cells/mm3 independent of growth factor support within the prior 3 months; Platelet count >=75,000/µL independent of transfusion and/or growth factor;support within the prior 3 months; Serum albumin >=3.0 g/dL;Serum creatinine <1.5 × upper limit of normal (ULN) or calculated creatinine;clearance >= 50 mL/min/1.73m2; Serum potassium >= 3.5 mmol/L; Total bilirubin < 1.5 × ULN (Subjects with Gilbert*s Syndrome may be enrolled;if the total bilirubin is < 3 mg/dL with predominance of indirect bilirubin); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <= 2.5 ×;ULN; Electrocardiogram showing QTc <= 480 msec;10. Any number of prior hormonal interventions [including 1st generation antiandrogens;(flutamide, bicalutamide, nicalutamide), CYP17 inhibitors (eg AA), 2nd generation;androgen antagonists (e.g. enzalutamide), steroids, estrogens, finasteride, dutasteride];for PC are allowed. These therapies, except for GnRH analogs, must have been;discontinued for minimally 4 weeks before first dose of study drug. Enzalutamide must;have been discontinued for minimally 8 weeks before first dose of study drug.;11. Ability to swallow study drug whole as a capsule/tablet;12. A man who is heterosexually active with a woman of childbearing potential must agree;to use a double barrier method of birth control such as a condom along with another;effective contraceptive method [partner using occlusive cap (diaphragm or;cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, contraceptive pill, contraceptive patch, IUD, tubal ligation or status post hysterectomy)]. All men;must also not donate sperm during the study and for 3 months after receiving the last;dose of study drug;13. Each subject must sign an informed consent document indicating that they understand;the purpose of and procedures required for the study and are willing to participate in the;study

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating;in the study.;1. Known brain metastases;2. Pathological finding consistent with small cell carcinoma of the prostate;3. Administration of an investigational agent within 4 weeks of Cycle 1 Day 1;4. Chemotherapy, or immunotherapy for the treatment of PC within 4 weeks of Cycle 1 day 1;5. Therapies that must be discontinued or substituted at least 4 weeks prior to Cycle 1 Day 1 include the following: Medications known to lower the seizure threshold (see Section 8.3); Herbal and non-herbal products that may decrease PSA levels (ie, saw palmetto, pomegranates or pomegranate juice); Medications known to induce drug metabolizing enzymes such as dexamethasone, rifampicin, carbamazepine, phenytoin, phenobarbital, St. John*s;wort, etc. (see Section 8.3); Potent inhibitors of CYP3A4 (see Section 9.3);6. Subjects currently treated with spironolactone;7. Subject has known allergies, hypersensitivity, or intolerance to prednisone or the excipients of prednisone, AA or JNJ-56021927 (refer to Investigator's Brochures for AA and JNJ-56021927 and package insert for Prednisone) ;8. Known hypersensitivity to Vitamin E;9. History of seizures or presence of a condition that may pre-dispose to seizure (eg, prior;stroke within 1 year prior to Cycle 1 Day 1, brain arteriovenous malformation,Schwannoma, meningioma, or other benign CNS or meningeal disease, which may require treatment with surgery or radiation therapy);10. Any prior malignancy (other than adequately treated basal cell or squamous cell skin;cancer, superficial bladder cancer, or any other cancer in situ currently in complete;remission) within 3 years prior to Cycle 1 Day 1;11. History or evidence for any of the following: severe or unstable angina or myocardial;infarction within 12 months prior to Cycle 1 Day 1, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), clinically significant;ventricular arrhythmias or New York Heart Association (NYHA) Class III to IV heart disease;12. Presence of uncontrolled hypertension (systolic BP >= 160 mmHg or diastolic BP >= 100;mmHg). Subjects with a history of hypertension are allowed, provided that BP is;controlled to within these limits by anti-hypertensive treatment;13. Presence of gastrointestinal disorder affecting absorption;14. History or evidence for adrenal insufficiency or hyperaldosteronism;15. Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis) or other;medical condition that would make prednisone (corticosteroid) use contraindicated;16. Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg;prednisone daily within 4 weeks prior to Cycle 1 Day 1 and up to Cycle 2 Day 8;17. Subject has any condition for which, in the opinion of the investigator, participation;would not be in the best interest of the subject (eg, compromise the well-being) or that;could prevent, limit, or confound the protocol-specified assessments;18. Subject is an employee of the investigator or study site, with direct involvement in the;proposed study or other studies under the direction of that investigator or study site, as;well as family members of the employees or the investigator.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective is to evaluate the effect of JNJ-56021927 on steady state<br /><br>abiraterone pharmacokinetics in subjects with Metastatic Castration-Resistant<br /><br>Prostate Cancer (mCRPC) during combination treatment of JNJ-56021927 with<br /><br>abiraterone acetate plus prednisone.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objectives of this study are:<br /><br>* To characterize the safety profile of JNJ-56021927 in combination with AAP<br /><br>* To evaluate clinical efficacy of JNJ-56021927 in combination with AAP<br /><br>* To characterize the pharmacokinetic (PK) profile of JNJ-56021927 when dosed<br /><br>in combination with AAP</p><br>