Researchers seek 600 men or women who are postmenopausal, or who have permanently stopped having their monthly period, who have hormone receptor-positive, HER2-negative breast cancer that spread to tissue, lymph nodes or another part of the body for a phase III study.
The trial team will assess whether the aromatase inhibitor exemestane (Aromasin) is more effective when given with entinostat, an HDAC inhibitor, than when given alone. HDAC inhibitors are a class of medicines that slows or stops an enzyme called histone deacetylase, HD, from helping cell growth.
Background and Goals
Estrogen stimulates cancer cells to divide and grow in hormone-positive breast cancer. Hormonal therapy using exemestane may lessen cancer growth by lowering the estrogen the body makes.
However, some advanced breast cancers can build a resistance to hormonal therapies like exemestane, causing them to stop working. In a phase II study, entinostat helped reverse resistance to AIs, which allowed exemestane to keep working. It does this by blocking the HD enzymes needed for cell growth.
Because of entinostat's success in phase II, the FDA labeled it a “breakthrough therapy,” which helped it move more quickly into phase III trials.
The researchers hope that adding entinostat to exemestane will help extend the time that exemestane works to slow or stop advanced breast cancer from growing or spreading further.
To do this, the trial team will measure progression-free survival, or PFS, of people taking exemestane with or without entinostat. PFS is the time from the start of treatment that the cancer does not worsen or spread. They will also measure overall survival, the time from the start of treatment to death from any cause, for up to 5 years and 10 months.
Participants will be randomly assigned to one of two groups:
- Exemestane plus entinostat: given an exemestane pill once a day on days 1-28 and an entinostat pill on days 1, 8, 15, and 22.
- Exemestane alone: given an exemestane pill once a day on days 1-28 and a placebo, an inactive pill, on days 1, 8, 15, and 22.
Men in both groups will also receive goserelin acetate on day 1, to lower their estrogen. Women who no longer get their periods already have low estrogen and these levels drop with AI treatment, so do not need goserelin acetate.
Courses will repeat every 28 days for both groups unless the disease worsens, side effects become too much or you or your doctor decide it is best to leave the trial.
This is a double-blind study, meaning you, your doctor and the researcher do not know which treatment you are getting.
Note: Sexually active males are advised to use birth control or avoid sexual intercourse during the study and for 3 months after therapy stops because fathering a child while taking goserelin acetate can cause birth defects.
You may be able to take part if you:
- are a man or woman age 18 or older
- If you are 55 years or older, you should not have had a period for more than a year
- If you are younger than 55, you should not have had a period in one or more years and must have a certain level of estradiol, a sex hormone.
- have a life expectancy of at least 12 weeks
- have received only 1 chemotherapy treatment, completed at least 3 weeks before the trial
- had cancer come back or worsen while on a non-steroidal aromatase inhibitor (anastrozole or letrozole)
You may not be able to take part if you:
- are receiving another anticancer therapy or experimental medicine
- have received any HDAC inhibitor before enrollment (for example, valproic acid, entinostat or vorinostat)
- have received prior exemestane or fulvestrant
- have brain metastases or a history of them
This study is being conducted in 51 US locations. For location details and contact information, visit ClinicalTrials.gov.