| Eligibility |
Inclusion Criteria:
- Provide informed consent
- Be able to communicate effectively with the study personnel
- Aged =18 years
- For Female Subjects Menopausal status
- Be postmenopausal as defined by the National Comprehensive Cancer Network as
either:
- Age =55 years and one year or more of amenorrhea
- Age <55 years and one year or more of amenorrhea, with an estradiol assay
<20 pg/mL
- Age <55 years and surgical menopause with bilateral oophorectomy
- Be premenopausal or perimenopausal with a negative urine pregnancy test.
- If subject is of child bearing potential, the subject must agree to use
acceptable methods of contraception:
- If female study participant could become pregnant, use acceptable methods of
contraception from the time of the first administration of study medication
until 6 months 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 of male partner (vasectomy with
documentation of azoospermia) and a barrier method {condom used with
spermicidal foam/gel/film/cream/suppository}
- If female study participant 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 study participant 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
- For Male Subjects
Subject 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 6
months 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 azoospermia) 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
- For premenopausal and perimenopausal women where exemestane monotherapy or
exemestane plus everolimus is chosen as the active control treatment or the
patient is randomized to receive sabizabulin, the patient must be already on
ovarian suppression or be candidates for this treatment: e.g., luteinizing
hormone release hormone agonist or ovariectomy
- Eastern Cooperative Oncology Group (ECOG) performance status of =2
- Documented evidence of ER+/HER2- metastatic breast cancer (NOTE: patients HER2+
metastatic breast cancer are excluded from participation in this study)
- Measurable disease is required as per RECIST 1.1 as confirmed by BICR (NOTE: Bone
only metastatic disease is acceptable but requires a measurable component)
- Received a nonsteroidal AI (monotherapy or combination therapy) either for
adjuvant or metastatic breast cancer and a SERD, such as fulvestrant (monotherapy
or combination therapy) for MBC; at least one of the non-steroidal AI or SERD
must have been given in combination with a CDK 4/6 inhibitor.
- Previously responded (without disease progression for at least 6 months) to one
of the following treatments: SERD monotherapy or SERD plus CDK 4/6 inhibitor or
nonsteroidal aromatase inhibitor monotherapy or nonsteroidal aromatase inhibitor
plus CDK 4/6 inhibitor for metastatic breast cancer.
- Subject is willing to comply with the requirements of the protocol through the
end of the study
Exclusion Criteria:
- Women of childbearing potential or fertile men with a female partner of childbearing
potential not willing to use effective contraception during the study and 6 months
after last dose of study drug for the women of childbearing potential participating in
the study and for 3 months after last dose of study drug in fertile men with a female
partner of childbearing potential.
- Known hypersensitivity or allergy to sabizabulin or colchicine
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 X upper limit
of normal (ULN) or total bilirubin >ULN (an elevated total bilirubin up to 1.5 X ULN
attributed to a previously confirmed diagnosis of Gilbert's disease is acceptable if
all other eligibility criteria are met). In patients with documented metastases to the
liver, the limits for inclusion are ALT or AST >5.0 X ULN or total bilirubin >1.5 X
ULN.
- Patients with biliary catheter
- Creatinine clearance < 60 mL/min as measured using the Cockcoft Gault formula
(patients with mild and moderate renal failure are not excluded from participation in
this study)
- QT interval corrected by Fridericia's formulation >480 ms
- Patients with history of Tosade de Pointe
- Patients taking QT-prolonging drugs
- Previously received >1 course of systemic chemotherapy (not including immunotherapies
or targeted therapies) for the treatment of metastatic breast cancer.
NOTE: A course of systemic chemotherapy is defined as a line of prior chemotherapy.
Chemotherapy received in the neoadjuvant or adjuvant setting will not count as a prior line
of chemotherapy.
- Subjects with radiographic evidence of central nervous system (CNS) metastases as
assessed by CT or MRI that are not well-controlled (symptomatic or requiring control
with continuous corticosteroid therapy [e.g., dexamethasone]) NOTE: Subjects with CNS
metastases are permitted to participate in the study if the CNS metastases are
medically well-controlled and stable for at least 30 days after receiving local
therapy (irradiation, surgery, etc.)
- Radiotherapy within 14 days prior to randomization except in case of localized
radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can
then be completed within 7 days prior to randomization. Subjects must have recovered
from radiotherapy toxicities prior to randomization
- Any comorbid disease or condition (medical or surgical) which might compromise the
hematologic, cardiovascular, endocrine, pulmonary, severe renal impairment,
gastrointestinal, hepatic, or central nervous system; or other conditions that may
interfere with the absorption, distribution, metabolism or excretion of study drug, or
would place the subject at increased risk
- Treatment with any investigational product within < 5 half-lives for each individual
investigational product OR within 30 days prior to randomization whichever is shorter.
- Major surgery within 30 days prior to randomization
- Treatment with testosterone, methyltestosterone, oxandrolone (Oxandrin®),
oxymetholone, danazol, fluoxymesterone (Halotestin®), testosterone-like agents (such
as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including
herbals), or antiandrogens (enzalutamide, abiraterone, bicalutamide, apalutamide, or
darolutamide). Previous therapy with testosterone and testosterone- like agents is
acceptable with a 30-day washout (if previous testosterone therapy was long term depot
within the past 6 months, the site should contact the Medical Monitor) or any other
androgenic agent.
- Treatment with any of the following hormone replacement therapies for metastatic
breast cancer. Prior use in the adjuvant or neoadjuvant setting is allowed if the
treatment is discontinued greater than 30 days prior to randomization
- Estrogens
- Megestrol acetate
- Testosterone
- All other concurrent anticancer treatments (including, but not limited to, all SERMs
unless randomized to the Control Treatment Group with a SERM as the control treatment,
AIs unless randomized to Control Treatment Group (exemestane or exemestane plus
everolimus) with the AI containing treatment as the control treatment, and all CDK 4/6
inhibitors)
- An abnormal ECG result which, based on the investigator's clinical judgment, would
place the subject at increased risk
- Has a known additional, invasive, malignancy that is progressing or required active
treatment in the last 5 years [note: subjects with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, ductal breast carcinoma in situ, bladder cancer
(superficial treated), or cervical carcinoma in situ that have undergone potentially
curative therapy are not excluded]
- Pregnant, lactating, or breastfeeding, or intending to become pregnant during the
study or within 60 days after the final dose of study treatment
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