A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men with Non-Metastatic (M0) Castration-Resistant Prostate Cancer
- Conditions
- Non-Metastatic Castration-Resistant Prostate Cancernon-spread Castration-Resistant Prostate Cancer10036958
- Registration Number
- NL-OMON54510
- Lead Sponsor
- Aragon Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 35
1. Criterion modified per amendment. 1.2 Histologically or cytologically
confirmed adenocarcinoma of the prostate without neuroendocrine differentiation
or small cell features, with high risk for development of metastases, defined
as PSADT <= 10 months. PSADT is calculated using at least 3 PSA values obtained
during continuous ADT. (see Section 5.1). 2. Criterion modified per amendment
2.1 Castration-resistant prostate cancer demonstrated during continuous ADT,
defined as 3 PSA rises at least 1 week apart, with the last PSA > 2 ng/mL 3.
Criterion modified per amendment 3.1. Criterion modified per amendment 3.2
Surgically or medically castrated, with testosterone levels of <50 ng/dL. If
the patient is medically castrated, continuous dosing with GnRHa must have been
initiated at least 4 weeks prior to randomization and must be continued
throughout the study to maintain castrate levels of testosterone. 4. Criterion
modified per amendment 4.1 Patients receiving bone loss prevention treatment
with bone-sparing agents indicated for the treatment of osteoporosis at doses
and dosing schedule appropriate for the treatment of osteoporosis (e.g.,
denosumab [Prolia®], zoledronic acid [Reclast®]) must be on stable doses for at
least 4 weeks prior to randomization. 5. Criterion modified per amendment 5.2
Patients who received a first generation anti-androgen (e.g., bicalutamide,
flutamide, nilutamide) must have at least a 4-week washout prior to
randomization AND must show continuing disease (PSA) progression (an increase
in PSA) after washout. 6. Criterion modified per amendment 6.2 At least 4 weeks
must have elapsed from the use of 5-a reductase inhibitors (e.g., dutasteride,
finasteride), estrogens (irrespective of dose used), and any other anti-cancer
therapy prior to randomization, including chemotherapy given in the
adjuvant/neoadjuvant setting (e.g., clinical trial) 7. At least 4 weeks must
have elapsed from major surgery or radiation therapy prior to randomization 8.
Age >= 18 years 9. Eastern Cooperative Oncology Group (ECOG) Performance Status
grade 0 or 1 10. Resolution of all acute toxic effects of prior therapy or
surgical procedure to Grade 1 or baseline prior to randomization 11. Criterion
modified per amendment 11.1 Criterion modified per amendment 11.2 Adequate
organ function as defined by the following criteria: * Serum aspartate
transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum
alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) <= 2.5 x
upper limit of normal (ULN) * Total serum bilirubin <=1.5 x ULN. Total serum
bilirubin >1.5 x ULN is allowed if Gilbert*s disease is documented prior to
screening. * Serum creatinine <= 2 x ULN * Absolute neutrophil count (ANC) >=
1500/µL * Platelets >= 100,000/µL * Hemoglobin >= 9.0 g/dL o Administration of
growth factors or blood transfusions will not be allowed within 4 weeks of the
hematology labs required to confirm eligibility 12. Signed and dated informed
consent document indicating that the patient (or legally acceptable
representative) has been informed of all pertinent aspects of the trial prior
to randomization 13. Criterion modified per amendment 13.1 Willingness and
ability to comply with scheduled visits, treatment plans, laboratory and
radiographic assessmen
1. Criterion modified per amendment 1.1 Presence of distant metastases
confirmed by blinded independent central review (BICR), including CNS and
vertebral or meningeal involvement, or history of distant metastases.
Exception: Pelvic lymph nodes <2 cm in short axis (N1) located below the
iliac bifurcation are allowed 2. Symptomatic loco-regional disease requiring
medical intervention, such as moderate or severe urinary obstruction or
hydronephrosis, due to primary tumor (e.g., tumor obstruction of bladder
trigone) 3. Prior treatment with second generation anti-androgens (e.g.,
enzalutamide) 4. Criterion modified per amendment 4.1 Prior treatment with
CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galerterone,
ketoconazole, aminoglutethimide) 5. Prior treatment with radiopharmaceutical
agents (e.g., Strontium-89), immunotherapy (e.g., sipuleucel-T), or any other
investigational agent for NM-CRPC 6. Prior chemotherapy for prostate cancer,
except if administered in the adjuvant/neoadjuvant setting 7. History of
seizure or condition that may pre-dispose to seizure (e.g., prior stroke within
1 year prior to randomization, brain arteriovenous malformation, Schwannoma,
meningioma, or other benign CNS or meningeal disease which may require
treatment with surgery or radiation therapy) 8. Criterion modified per
amendment 8.1 Criterion modified per amendment 8.2 Concurrent therapy with any
of the following (all must have been discontinued or substituted for at least 4
weeks prior to randomization): * Medications known to lower the seizure
threshold (for a complete list please see Appendix 5) * Herbal (i.e., saw
palmetto) and non-herbal products (i.e., pomegranate) that may decrease PSA
levels * Systemic (oral/IV/IM) corticosteroids. Short term use (<= 4 weeks) of
corticosteroids during the study is allowed if clinically indicated, but it
should be tapered off as soon as possible * Any other experimental treatment on
another clinical trial * Agents indicated for the prevention of
skeletal-related events in patients with solid tumors (e.g., denosumab
[Xgeva®]) 9. Criterion modified per amendment 9.1 Criterion modified per
amendment 9.2 History or evidence of any of the following conditions: - 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 5 years prior to randomization * Any of the
following within 6 months prior to randomization:Severe/unstable angina,
myocardial infarction, symptomatic congestive heart failure, arterial or venous
thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident
including transient ischemic attacks), or clinically significant ventricular
arrhythmias - Uncontrolled hypertension (systolic blood pressure >=160 mmHg or
diastolic BP >=100 mmHg). Patients with a history of uncontrolled hypertension
are allowed provided blood pressure is controlled by anti-hypertensive
treatment. -Gastrointestinal disorder affecting absorption -Active infection,
such as human immunodeficiency virus (HIV) - Any other condition that, in the
opinion of the Investigator, would impair the patient*s ability to comply with
study procedures.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Metastasis-Free Survival (MFS)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints<br /><br>* Time to Metastasis (TTM)<br /><br>* PFS<br /><br>* Time to symptomatic progression<br /><br>* Overall survival (OS)<br /><br>* Time to initiation of cytotoxic chemotherapy<br /><br><br /><br>Other Evaluations<br /><br>* Health-related quality of life and prostate cancer-specific symptoms<br /><br>* Type, incidence, severity, timing, seriousness, and relatedness of adverse<br /><br>events and laboratory abnormalities<br /><br>* PSA Response<br /><br>* Time to PSA progression<br /><br>* Population PK<br /><br>* Assessment of ventricular repolarization<br /><br>* Second progression-free survival (PFS2)<br /><br>* Medical resource utilization (MRU)</p><br>