Advanced or recurrent breast cancer
Conditions
Interventions
investigational material(s)
Generic name etc : KHK2375 and EXE001
INN of investigational material : entinostat and exemestane
Therapeutic category code : 429 Other antitumor agents
Dosage and Administ
Sponsors
Kyowa Kirin Co., Ltd.
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1) Personally submitted voluntary written informed consent to participate in the study 2) Age >= 20 years at the time of consent 3) Histologically or cytologically confirmed breast cancer positive for estrogen receptor (ER) and/or progesterone receptor (PgR) 4) Human epidermal growth factor 2 (HER2)-negative 5) Stage III/locally advanced or metastatic carcinoma of the breast where local therapy with curative intent is impossible 6) Pre/Peri- and postmenopausal women Postmenopausal status is defined either by: - Age >= 55 years and >= 1 year of amenorrhea - Age = 1 year of amenorrhea, with blood estradiol (E2) = 9.0 g/dL - Platelet count: >= 100000/uL - Neutrophil count: >= 1500/uL - Serum creatinine: =< 2.0 mg/dL - Total bilirubin in serum: < 1.5 X institutional upper limit of normal (=< 3 mg/dL for subjects with Gilbert's syndrome) - AST and ALT: =< 3.0 X institutional upper limit of normal
Exclusion criteria
Exclusion criteria: 1) Endocrine therapy (except for LH-RH agonist), treatment with everolimus, treatment with a cyclin-dependent kinase inhibitor, or radiation therapy within 14 days before enrollment Subjects with prior treatment with exemestane may be enrolled if they meet either of the following criteria: - Start of treatment with exemestane for advanced or recurrent breast cancer within 28 days before enrollment - Recurrence-free period >12 months after completion of treatment with exemestane as postoperative adjuvant therapy For painful bone lesions or impending fractures, radiation therapy may be used concomitantly if there is a measurable or nonmeasurable lesion that is suitable for efficacy evaluation in a region other than the radiation field 2) Two or more prior chemotherapy regimens for advanced or recurrent breast cancer 3) Chemotherapy within 21 days before enrollment 4) Treatment with bisphosphonates or anti-RANKL antibody that is scheduled to be started within 7 days before the first dose of investigational product 5) History of or current central nervous system metastasis, or current leptomeningeal or periosteal disease 6) History of cancer other than breast cancer within 5 years, or concurrent cancer other than breast cancer (except for basal cell carcinoma of skin, squamous cell carcinoma of skin, and intraepithelial carcinoma of uterine cervix) Subjects continuing to receive treatment for cancer other than breast cancer are ineligible for enrollment 7) Ongoing treatment with any other anticancer therapy or investigational product (Except for treatment with exemestane or radiotherapy as described in exclusion criterion 1) 8) Prior treatment with histone deacetylase inhibitor (e.g. valproate, vorinostat) 9) Known allergy to imidazoles, exemestane, or entinostat 10) Any medical or psychiatric condition that could affect compliance with the protocol, ability to give consent, or assessment of anticipated toxicities 11) Uncontrolled complications (e.g., active infections) 12) Positive for either hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus antibody 13) Any other conditions unsuitable for the study in the opinion of the investigator or subinvestigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Progression-free survival (PFS) The primary objective is to investigate the effect of 5 mg KHK2375 on progression free survival (PFS) when administered orally at weekly intervals in combination with exemestane in a placebo-controlled, double-blind comparative study in subjects with advanced or recurrent hormone receptor-positive breast cancer. | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Overall survival (OS) Antitumor effect The secondary objectives are to investigate the effect of KHK2375 on overall survival (OS) and the antitumor effect of KHK2375 when administered orally at a dose of 5 mg at weekly intervals in combination with exemestane and to evaluate the safety of the combination therapy in a placebo-controlled, double-blind comparative study in subjects with advanced or recurrent hormone receptor-positive breast cancer. | — |
Countries
Japan
Outcome results
None listed