A Phase 1/2 Open-label Study to Assess the Safety, Pharmacokinetics, and Anti-tumor Activity of Oral EPI-506 in Patients with Metastatic Castration-resistant Prostate Cancer
- Conditions
- Metastatic Castration-Resistant Prostate CancerMedDRA version: 18.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004764-10-GB
- Lead Sponsor
- Essa Pharmaceuticals Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 166
Parts I and II
Inclusion Criteria
Patients are eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)/Independent Ethics
Committee (IEC)-approved written informed consent and
privacy language as per national regulations must be
obtained from the patient prior to any study-related
procedures being performed.
2. Male 18 years of age or older.
3. Histologically confirmed adenocarcinoma of the prostate
without known neuroendocrine differentiation or small cell
features.
4. PSA progression within 8 weeks of study treatment
(requires a baseline and minimum of 2 sequentially rising
PSA levels at an interval of = 1 week between each
determination while taking androgen deprivation therapy
[ADT])
5. Presence of metastatic disease at study entry documented
by 1 or more bone lesions on bone scan or by soft tissue
disease observed by CT/MRI.
6. Asymptomatic or minimally symptomatic patients defined
as reported pain score on BPI-SF question #3 (worst pain in
prior 24 hours) must be < 4 at screening.
7. Disease progression while receiving abiraterone or
enzalutamide as assessed by either:
a. PSA progression;
b. Radiographic progression with 2 new lesions on bone
scan or soft tissue progression on CT/MRI per
mRECISTv1.1.
8. The patient must have recovered from toxicities related to
any prior treatments, unless toxicities are assessed by the
Investigator as clinically non-significant (e.g., hot flashes
from luteinizing-hormone receptor hormone (LHRH)
therapy).
9. Castrate at screening:
a. Ongoing ADT with LHRH agonist/antagonist therapy
or history of bilateral orchiectomy.
b. Serum testosterone = 1.7 nmol/L (50 ng/dL) at
screening.
10. Patients receiving bisphosphonates or other approved bonetargeting
therapy (e.g., denosumab) must be on a stable
dose for at least 4 weeks prior to the start of study drug.
11. PSA value at screening = 2 ng/mL.
12. Life expectancy of = 6 months according to the
Investigator’s judgment.
13. Eastern Cooperative Oncology Group (ECOG)
performance status score of 0 to 1.
14. All sexually active patients are required to use a condom as
well as meet 1 of the following:
a. Patient is non-fertile (orchiectomy), or has a female
partner of non-childbearing potential (i.e., postmenopausal,
surgically sterilized, hysterectomy)
b. Patient and his female partner use must agree to use
an adequate contraceptive method from the first day
of dosing until 3 months after the last dose to prevent
pregnancies. Adequate contraceptive method is
defined as:
i. Established use of oral, injected, or impl
Parts I and II
Exclusion Criteria
Patients will be excluded from participation in the study if any
of the following apply:
1. Candidates for cytotoxic chemotherapy or have received a
biologic anti-cancer therapy (e.g., sipuleucel-T, docetaxel,
cabazitaxel, and estramustine) or a cytotoxic chemotherapy
within 4 weeks prior to the start of study drug.
2. Have received more than 1 line of chemotherapy for the
treatment of mCRPC.
3. Use of hormonal agents with anti-tumor activity against
prostate cancer including 5-alpha reductase inhibitors,
androgens (e.g., testosterone), cytoproterone acetate,
progestational agents, and estrogens/diethylstilbestrol
within 4 weeks prior to the start of study drug. Low-dose
hormonal agents (e.g., Megace) given for treatment of side
effects of LHRH therapy are allowed with prior approval
from the Medical Monitor.
4. Use of bicalutamide or nilutamide within 6 weeks prior to
the start of study drug, and flutamide within 4 weeks prior
to the start of study drug.
5. Use of an investigational agent that targets the AR axis (i.e.,
AR antagonists, AR signaling inhibitors, agents that target
alternative blockade of the AR, and androgen synthesis
inhibitory agents).
6. Enzalutamide and/or abiraterone use as follows:
a. Received more than 1 treatment course of
enzalutamide
b. Received more than 1 treatment course of abiraterone
c. Received either agent within 4 weeks prior to the start
of study drug.
d.
Received abiraterone and/or enzalutamide and
discontinued agent without evidence of radiographic
or PSA progression.
7. Use of systemic corticost eroids exceeding prednisone 10 mg/day within 4 weeks prior to the start of study drug.
Increased dose of inhaled steroids may be allowed with
approval by a study Medical Monitor.
8. Use of prior radionuclide (e.g., strontium-89 or samarium).
9. Use of radium-223 dichloride within 28 days prior to the
start of study drug.
10. Received limited-field palliative bone radiotherapy
> 5 fractions and/or any radiotherapy within 2 weeks prior
to the start of study drug.
11. Received a blood transfusion within 28 days of screening.
12. Major surgery within 2 months prior to screening.
13. Known intra-cerebral disease or brain metastasis.
14. Spinal cord compression as follows:
a. Candidates with spinal cord compression related to
prostate cancer that required treatment within 6
months prior to starting study drug.
b. Any symptoms of neurologic compromise with
radiographic evidence of potential spinal cord
compression within 4 weeks prior to starting study
drug.
15. Diagnosis of another invasive malignancy
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method