Advanced ChemoHormonal Therapy for Treatment Naive Metastatic Prostate Cancer
- 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
- 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
I. Efficacy of apalutamide in combination with abiraterone acetate + prednisone following docetaxel with ongoing androgen deprivation therapy in men with high risk metastatic castration sensitive disease.
I. Safety and tolerability of apalutamide in combination with abiraterone acetate + prednisone following docetaxel with ongoing androgen deprivation therapy.
II. Time to event.
III. Depth of prostate specific antigen (PSA) response.
I. Quality of life.
Patients receive apalutamide orally (PO) once daily (QD), abiraterone acetate PO QD, and prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of care.
After completion of study treatment, patients are followed up every 6 months for up to 10 years.
Trial Phase Phase II
Trial Type Treatment
OHSU Knight Cancer Institute
Julie Nicole Graff
- Primary ID STUDY00016728
- Secondary IDs NCI-2020-00598
- Clinicaltrials.gov ID NCT04267887