| Eligibility |
Inclusion Criteria:
- All patients must have a histologically or cytologically proven diagnosis of
adenocarcinoma of the prostate. (Note: Gleason score not required if biopsy of
metastasis was used to make the histologic diagnosis)
- All patients must have metastatic disease: either soft tissue and/or bony metastases
prior to initiation of androgen. Measurable disease is not required
- Baseline imaging must have been performed within 42 days before or 14 days after
initiating luteinizing hormone releasing hormones (LHRH) therapy. All disease must be
assessed and documented on the Baseline Tumor Assessment Form
- Patients may have started on LHRH therapy for metastatic prostate cancer provided this
was initiated no longer than 60 days prior to registration
- Patients may have received neoadjuvant and/or adjuvant LHRH therapy during
definitive treatment or salvage radiation; if so at least 12 months must have
elapsed from the last LHRH injection and baseline testosterone must be > 150
ng/dL
- No restriction on bicalutamide used for flare prevention or combined therapy
however bicalutamide must be stopped at registration
- Patients must have a Karnofsky performance status of 60 - 100
- Men of reproductive potential and those who are surgically sterilized (i.e.,
vasectomy) must agree to practice effective barrier contraception or agree to abstain
from intercourse while receiving treatment on this study and for at least 4 months
after protocol treatment ends
- Bilirubin =< 2 x institutional upper limit of normal (ULN) (obtained within 28 days
prior to registration)
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x
institutional ULN, or =< 5 x institutional ULN if liver metastases are present
(obtained within 28 days prior to registration)
- Calculated creatinine clearance >= 30 mL/min using a serum creatinine obtained within
28 days prior to registration
- Leukocytes >= 3,000/mcL (obtained within 28 days prior to registration)
- Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 28 days prior to
registration)
- Hemoglobin >= 9 g/dL (obtained within 28 days prior to registration)
- Platelets >= 100,000/mcL (obtained within 28 days prior to registration)
- All subjects must have the ability to understand and the willingness to sign a written
informed consent
- Patients may have received prior androgen deprivation therapy (ADT) -neoadjuvant
and/or adjuvant, or in conjunction with salvage radiation - but it must not have
lasted for more than 36 months. Single or combination therapy allowed. At least 6
months must have elapsed since completion of androgen deprivation therapy in the
neoadjuvant and/or adjuvant setting, and serum testosterone must be > 150 ng/mL within
28 days prior to registration. Note: Serum testosterone assessment is required for
eligibility for only those with prior treatment with ADT
- Patients who have already started on LHRH therapy are eligible, provided no more
than 60 days have elapsed from LHRH injection (or surgical castration) for
metastatic prostate cancer prior to registration. The start date of medical
castration is considered the day the patient first received an injection of a
LHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen. Subjects may
not already be taking abiraterone, enzalutamide, apalutamide or other
intensification agent during this time - bicalutamide is permitted
- Patients may have received palliative radiotherapy for symptomatic bone or visceral
metastasis, provided they have recovered from all side effects at the time of
registration
- Patients may have received prior surgery. For all major surgeries, at least 14days
must have elapsed since completion and patient must have recovered from all major side
effects of surgery per investigator's assessment
- Patients may have received or plan to receive concurrent bone targeting agents that do
not have an effect on prostate specific antigen (PSA) (e.g. denosumab or
bisphosphonate)
Exclusion Criteria:
- Patients must not have received prior and/or must not have any plans for receiving
concomitant therapy with ketoconazole, aminoglutethimide, or enzalutamide (MDV3100).
Concurrent megestrol for hot flashes is allowed
- Patients must not have received any prior cytotoxic chemotherapy for metastatic
prostate cancer
- Prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant
setting may be allowed at the discretion of the principal investigator. At least
2 years must have elapsed since completion of cytotoxic chemotherapy in the
neoadjuvant and/or adjuvant setting
- Patients with known brain metastases are not eligible. Brain imaging studies are not
required for eligibility if the patient has no neurologic signs or symptoms suggestive
of brain metastasis. But, if brain imaging studies are performed, they must be
negative for disease
- Patients must not have New York Heart Association class III or IV heart failure at the
time of screening. Patients must not have any thromboembolic event, unstable angina
pectoris, myocardial infarction, or serious uncontrolled cardiac arrhythmia within 6
months prior to registration
- Patients must not have uncontrolled hypertension (defined as blood pressure > 160 mmHg
systolic and > 90 mmHg diastolic at 2 separate measurements no more than 60 minutes
apart) despite appropriate medical therapy. Note: Patients may be rescreened after
adjustments of antihypertensive medications
- Patients must not be known to have human immunodeficiency virus (HIV) infection,
active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any
serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with participation in this study
- Patients with a known history of primary and secondary adrenal insufficiency are not
eligible
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to any of the study drugs
- Patients may not be receiving any other investigational agents, or concurrent
biological, chemotherapy, or radiation therapy. Previous experimental therapy must
have been completed at least 28 days prior to registration
- Patients must not have known gastrointestinal (GI) disease or GI procedure that could
interfere with the GI absorption or tolerance of any of the study drugs, including
difficulty swallowing oral medications
- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, adequately treated stage I or II cancer from
which the patient is currently in complete remission, or any other cancer from which
the patient has been disease-free for 5 years
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