This research study is studying a combination of drugs as a possible treatment for
castration-resistant prostate cancer.
The interventions involved in this study are:
- Docetaxel (a type of chemotherapy)
- Apalutamide (the study medication, also known as ARN-509)
- Prednisone (a corticosteroid given to prevent reactions to docetaxel).
- Leuprolide acetate (also known as Lupron, a GnRH agonist or similar drug which is
standard of care, causes chemical castration which greatly lowers the level of
testosterone in the body)
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational intervention to learn whether the intervention works
in treating a specific disease. "Investigational" means that the intervention is being
Apalutamide is considered an investigational product, which is believed to reduce the growth
of prostate cancer cells. The FDA (the U.S. Food and Drug Administration) has not approved
apalutamide as a treatment for any disease, but it is being studied in prostate cancer.
Docetaxel is an approved therapy for this type of cancer. The FDA has not approved the
combination of the two drugs in any use.
In this research study, the investigators are evaluating the combination of two drugs,
docetaxel with apalutamide. The investigators will keep track of participants'
prostate-specific antigen (PSA), scans, and overall health to determine how well this drug
combination works at treating this type of cancer.
- Histologically confirmed adenocarcinoma of the prostate
- Castration-resistant prostate cancer requires the following criteria:
- A castrate level of testosterone (< 50ng/dL)
- Prostate cancer progression on or since last treatment as documented by PSA rise
or bone progression according to PCWG2 or soft tissue radiographic progression
according to RECIST criteria Version 1.1
- If on anti-androgen, will need to show no PSA decline after at least a 6 week
withdrawal period from the last dose of bicalutamide or nilutamide or 4 weeks
from last flutamide dose
- Will require a 2 week washout period from last dose of ketoconazole, abiraterone
acetate or radiation
- Treatment with abiraterone acetate for CRPC in the past is required. Does not need to
be the last treatment prior to enrollment.
- There is no limit to number of prior therapies
- Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix
- Adequate organ function as evaluated by the following laboratory criteria:
- Hemoglobin ≥ 9g/dL; no transfusions and erythropoietin supplementation permitted
within the last 3 months
- Absolute neutrophil count (ANC) ≥ 1500/µL
- Platelet count ≥ 100 x 10^9/L
- Total bilirubin ≤ upper limit of normal (ULN, Note: In subjects with Gilbert's
syndrome, if total bilirubin is ≥ 1.5 × ULN, measure direct and indirect
bilirubin and if direct bilirubin is ≤ ULN, subject may be eligible)
- AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis
- Serum creatinine < 2.0 × ULN or creatinine clearance > 30cc/min
- Serum albumin ≥ 3.0 g/dL
- Serum potassium ≥ 3.5 mmol/L (if < 3.5, can be repleted and reassess for
eligibility as long as stable off potassium supplementation for > 48 hrs)
- Ability to swallow the study drug as a whole tablet
- The effects of apalutamide and docetaxel on the developing human fetus are unknown.
For this reason and because chemotherapeutic agents are known to be teratogenic, men
must agree to use adequate contraception. Specifically, they must agree 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 agree 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. They 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.
- Pathology consistent with majority of specimen having small cell carcinoma of the
prostate (prostate cancer with neuroendocrine features is acceptable).
- Prior treatment with enzalutamide for CPRC; non-CRPC use allowed (e.g., neoadjuvant,
combined with radiation for localized disease and didn't progress while on it in those
- Prior treatment with docetaxel chemotherapy except if > 12 months since it was given
in either the neoadjuvant or adjuvant setting or for hormone sensitive disease (e.g.,
- Presence of untreated brain metastasis
- Seizure or known condition that may pre-dispose to seizure (including but not limited
to prior stroke, transient ischemic attack within 1 year prior to randomization, brain
arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas
that are causing edema or mass effect). Loss of consciousness within 12 months may be
permitted upon discussion with study PI.
- Medications known to lower the seizure threshold must be discontinued or substituted
at least 4 weeks prior to study entry.
- Current, recent (within 4 weeks of the first dose of this study), or planned
participation in an experimental drug study
- Persistent grade > 1 (NCI CTCAE v4.0) AEs due to investigational drugs that were
administered more than 14 days before study enrollment.
- Radiation within 2 weeks prior to entering the study
- Peripheral neuropathy ≥ Grade 2.
- Current evidence of any of the following:
- Uncontrolled hypertension
- Gastrointestinal disorder affecting absorption
- Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) or
other medical condition that would make prednisone/prednisolone (corticosteroid)
- Uncontrolled intercurrent illness including, but not limited to, severe or unstable
angina, myocardial infarction, symptomatic congestive heart failure (defined as New
York Heart Association Grade II or greater), arterial or venous thromboembolic events
(e.g., pulmonary embolism), or clinically significant ventricular arrhythmias,
significant vascular disease (e.g. aortic aneurysm, aortic dissection), or symptomatic
peripheral vascular disease within 6 months prior to randomization.
- Psychiatric illness/social situations that would limit compliance with study
- Any condition that in the opinion of the investigator, would preclude participation in
- History of allergic reactions or severe hypersensitivity reactions to drugs formulated
with polysorbate 80 or antisense oligonucleotides.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to apalutamide or docetaxel
- Participants receiving any medications or substances that are strong inhibitors or
inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly
changing, it is important to regularly consult a frequently-updated list such as
http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as
the Physicians' Desk Reference may also provide this information. As part of the
enrollment/informed consent procedures, the patient will be counseled on the risk of
interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or herbal
- Inability to comply with study and/or follow-up procedures