Advanced ChemoHormonal Therapy for Treatment Naïve Metastatic Prostate Cancer: Apalutamide and Abiraterone Acetate With Prednisone and Androgen Deprivation Therapy After Treatment With Docetaxel and Androgen Deprivation Therapy

Condition: Castration-Sensitive Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04267887

Sponsor: OHSU Knight Cancer Institute

Phase: Phase 2


  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed prostate cancer OR a strong suspicion of prostate cancer as evidenced by metastatic disease in a pattern consistent with prostate cancer (such as blastic lesions on a nuclear medicine bone scan or lymphadenopathy on the computed tomography [CT] scan) AND a PSA > 50 ng/mL
  • High risk disease (defined as meeting 2 of the 3: (1) visceral metastatic disease, (2) 3 or more bone lesions, (3) Gleason 8-10) at the time diagnosed metastatic
  • If a patient has received androgen deprivation therapy (ADT) for neoadjuvant or adjuvant therapy at least 24 months MUST have elapsed since its use to day 1 of restarting ADT for metastatic castration sensitive disease
  • ADT sensitive disease- no evidence of rising PSA or new metastatic deposits since starting ADT
  • Have completed up to 6 cycles of docetaxel since developing metastatic castration sensitive disease with no more than 12 weeks elapsed since day 21 of the final cycle
  • All races and ethnic groups will be included
  • Life expectancy of greater than 18 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin > 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
  • Leukocytes > 3,000/uL
  • Absolute neutrophil count > 1,500/uL
  • Platelets >= 100,000 x 10^9/uL, independent of transfusion and/or growth factors within 3 months prior to randomization
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Albumin > 3 g/dL
  • Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m^2; per Modification of Diet in Renal Disease (MDRD) calculation or institutional standard
  • Serum potassium >= 3.5 mmol/L
  • Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to day 1 of study
  • 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
  • Ability to understand, and the willingness to sign, a written informed consent document, as well as comply with study requirements

Exclusion Criteria:

  • Subjects who are unwilling to stop taking saw palmetto, PC-SPECs or other herbal agents known to affect the PSA
  • Patients may not have received any other investigational agents within 30 days prior to day 1 of study
  • Prior exposure to apalutamide, enzalutamide, abiraterone acetate, darolutamide, or any other second-generation androgen receptor antagonist
  • Note: prior exposure to bicalutamide, flutamide, nilutamide, or any other first-generation androgen receptor antagonist is permitted. No washout is required. Subjects may be on one of these at the time of consent, but it must be stopped prior to day 1 of study treatment. These drugs are frequently used in the newly diagnosed metastatic setting to blunt the effect of the testosterone spike
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide or other agents used in the study
  • Conditions that would interfere with treatment with docetaxel chemotherapy in the opinion of the treating physician (e.g. significant neuropathy)
  • Subject has another active malignancy other than non-melanomatous skin cancer (unless it is metastatic) or superficial bladder cancer
  • Either of the following:
  • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
  • Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure or left ventricular ejection fraction < 50%, arterial or venous thromboembolic events (e.g. pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to day 1 of study
  • Current evidence of any of the following:
  • Uncontrolled hypertension
  • Gastrointestinal disorder affecting absorption
  • Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis)
  • Any chronic medical condition requiring a higher dose of corticosteroid than a total of 10 mg prednisone/prednisolone daily
  • Any condition that in the opinion of the investigator, would preclude participation in this study.
  • Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day).
  • 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
  • Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)
  • Inability to stop a prohibited medication:
  • Atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone)
  • Bupropion
  • Lithium
  • Meperidine and pethidine
  • Phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine)
  • Tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine
  • Tramadol

View trial on ClinicalTrials.gov