This study is a multicenter, randomized, open-label, active-control, efficacy and safety
study of VERU-111 (Sabizabulin) for the treatment of metastatic castration-resistant prostate
cancer in patients who have failed prior treatment with at least one androgen receptor
targeting agent.
Subjects will have failed treatment with at least one prior androgen receptor targeting agent
and be eligible for treatment with an alternative androgen receptor targeting agent (as per
the current standard of care for these patients).
Subjects will be randomized in a 2:1 ratio to receive VERU-111 or Active Control (alternative
androgen receptor targeting agent).
Subjects in the VERU-111 treated group will receive VERU-111 32 mg per day orally with an
option to reduce the dose to 26 mg per day based on tolerability to the 32 mg dose until
radiographic progression (blinded independent central read) in observed. Subjects in the
Control treated group will receive an alternative androgen receptor targeting agent with dose
and dosing regimen defined in the FDA approved prescribing information until radiographic
progression in observed.
Randomization will be stratified by measurable disease vs. bone-only disease. A significant
proportion (>30%) of the patients randomized into the study will have measurable disease at
baseline.
Randomization will also be stratified by if the patient has failed one vs. more than one
prior androgen targeting agent.
The primary efficacy endpoint of the study will be radiographic progression free survival.
Inclusion Criteria:
- Provide informed consent.
- Be able to communicate effectively with the study personnel.
- Aged ≥18 years.
- Histological or cytologic proof of adenocarcinoma of the prostate not including the
diagnosis of small cell carcinoma of the prostate of neuroendocrine pathology.
- Radiographic evidence of metastatic disease at baseline by CT scan, or MRI and bone
scan, with confirmation of measurable disease by RECIST 1.1 and/or identifiable
discrete bone metastases by PCWG3.
- Known castration resistant prostate cancer, defined according to PCWG3 criteria.
- Have received at least one androgen receptor targeting agent (e.g. abiraterone,
enzalutamide, darolutamide, or apalutamide).
- Subjects who have metastatic castration resistant prostate cancer that have maintained
ADT and have failed prior treatment with at least one androgen receptor targeting
agent (abiraterone,enzalutamide, darolutamide, or apalutamide) defined as:
- Serum PSA progression of two consecutive increases in PSA over a previous reference
value within 6 months of first study treatment, each measurement at least 2 weeks
apart. Or
- Documented bone lesions by the appearance of two or more new lesions on bone
scintigraphy or bi-dimensionally-measurable soft tissue metastatic lesion assessed by
CT or MRI.
- Treatment with an alternative androgen receptor targeting agent is a reasonable next
line of therapy.
- Absolute PSA ≥2.0 ng/ml at screening.
- ECOG performance status <2.
- Participants must have normal organ and bone marrow function measured within 30 days
prior to administration of study treatment as defined below:
- Hemoglobin ≥9.0 g/dL with no blood transfusion in the past 30 days
- Creatinine clearance ≥60 mL/min
- Absolute neutrophil count (ANC) ≥1.5 x 109/L
- Platelet count ≥100 x 109/L
- Total bilirubin ≤ upper limit of normal (ULN) (or <2.5 x ULN for patients with known
Gilberts disease)
- Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase
(SGOT))/Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT))
≤2.5 x ULN. NOTE: Patients with elevations in bilirubin, AST, or ALT should be
thoroughly evaluated for the etiology of this abnormality prior to entry and patients
with evidence of viral infection should be excluded. Patients with chronic renal stent
and stable creatinine elevation can be included in the study with written
documentation from the PI.
- Participants must have a life expectancy >3 months.
- Subjects must agree to use acceptable methods of contraception:
- If the study subject's partner could become pregnant, use acceptable methods of
contraception from the time of the first administration of study medication until
6months following administration of the last dose of study medication. Acceptable
methods of contraception are as follows: Condom with spermicidal
foam/gel/film/cream/suppository [i.e.,barrier method of contraception], surgical
sterilization (vasectomy with documentation of azospermia) and a barrier method
{condom used with spermicidal foam/gel/film/cream/suppository}, the female partner
uses oral contraceptives (combination estrogen/progesterone pills), injectable
progesterone or subdermal implants and a barrier method (condom used with spermicidal
foam/gel/film/cream/suppository).
- If female partner of a study subject has undergone documented tubal ligation (female
sterilization), a barrier method (condom used with spermicidal
foam/gel/film/cream/suppository)should also be used.-If female partner of a study
subject has undergone documented placement of an intrauterine device (IUD) or
intrauterine system (IUS),a barrier method (condom with spermicidal
foam/gel/film/cream/suppository)should also be used.
- Other than metastatic prostate cancer, no evidence (within 5 years) of prior
malignancies (except successfully treated basal cell or squamous cell carcinoma of the
skin or other cancers treated with curative intent >3 years prior).
- Participants must agree to refrain from prolonged exposure to the sun or agree to use
at least SPF 50 on all exposed skin and protective clothing during prolonged sun
exposure throughout participation in this study and/or treatment with VERU- 111.
- Subject is willing to comply with the requirements of the protocol through the end of
the study.
Exclusion Criteria:
- Known hypersensitivity or allergy to colchicine.
- Histologic identification of small cell carcinoma of the prostate or neuroendocrine
pathology in either biopsy or prostatectomy tissue.
- A bone scan with evidence of superscan or superscan phenomenon, defined as:
- Uptake throughout the axial skeleton and proximal appendicular skeleton, often
somewhat heterogeneous, or,
- Symmetrically intense and diffuse radiotracer uptake in the skeleton with absent or
diminished visualization of the genitourinary system and soft tissues, or,
- Defined in the bone scan report as a superscan or superscan phenomenon. NOTE: Medical
Monitor should be consulted prior to screening of a patient if a superscan or
superscan phenomenon is suspected or possible, but undetermined by any of the above
definitions.
- Has received external-beam radiotherapy within the last 2 weeks prior to start of
study treatment.
- Patients with a QT interval corrected by Fridericia's formula of >480 ms.
- Patients receiving full dose warfarin therapy are not eligible for study.
- Patients with prior history of a thromboembolic event within the last 6 months.
- Participation in another clinical study with an investigational product during the
last 6 months prior to randomization into this study.
- Patients should be excluded if they have had prior systemic treatment with prior
taxane chemotherapies (for greater than 2 cycles) for advanced prostate cancer.
Patient can have up to 2 cycles of prior taxane chemotherapy greater than one year
prior to randomization and remain eligible for inclusion in this study. Taxane
exposure in the adjuvant or neoadjuvant setting is allowed (maximum of 6 cycles).
- Any treatment modalities involving major surgery within 4weeks prior to the start of
study treatment.
- Patients are excluded if they have known brain metastases or leptomeningeal
metastases.
- Patients should be excluded if they have a positive test for hepatitis B virus surface
antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating
acute or chronic infection.
- Has imminent or established spinal cord compression based on clinical findings and/or
MRI.
- Any other serious illness or medical condition that would, in the opinion of the
investigator, make this protocol unreasonably hazardous. Active infections discovered
during screening period must be treated and controlled before patient is dosed with
VERU-111.
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)
caused by previous cancer therapy, excluding alopecia.
- Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant
systemic disease or active, uncontrolled infection. Examples include, but are not
limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial
infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung
disease, or any psychiatric disorder that prohibits obtaining informed consent.
- Total bilirubin levels > 1.5 x ULN (>2.5 x ULN in patients with known Gilbert's
disease).
- AST and/or ALT levels >2.5xULN or AST and/or ALT levels >1.5xULN WITH concomitant
alkaline phosphatase levels >2.5xULN.
