This research study is a Phase II clinical trial, which tests the safety and effectiveness of
an investigational combination of drugs to learn whether they work in treating a specific
cancer. "Investigational" means that the combination of drugs is still being studied and that
research doctors are trying to find out more about it, such as the safest dose to use and the
side effects they may cause. It also means that the FDA has not yet approved the combination.
The two drugs being tested in this study are tivozanib and enzalutamide. Enzalutamide has
been approved by the FDA for treatment of prostate cancer. On the other hand, tivozanib is
still investigational, and has not been tested in a combination with enzalutamide before.
Enzalutamide is an androgen receptor antagonist (it blocks the activity of the male sex
hormones). Prostate cancers are initially dependent on the male hormone testosterone for
growth. Hormonal therapies that lower testosterone or block the ability of testosterone to
act at the level of the prostate cancer are currently among the most effective treatments for
prostate cancers taht have spread to other body organs (metastasized). The effectiveness of
hormonal treatments, however, is not permanent, and over time many prostate cancers progress
in spite of these treatments. Enzalutamide is a drug that has been proven to help delay the
progression of advanced prostate cancer on average for about 8 months.
Tivozanib is an anti-angiogenesis medicine that fights different types of cancer by blocking
the blood supply to the tumor, so that the tumor does not receive the nutrients it needs to
grow. The main goal of this study is to determine whether the combination of tivozanib and
enzalutamide is more effective in delaying the progression of disease than when enzalutamide
is given alone. This study will also determine whether treatment with the combination of the
tivozanib and enzalutamide will have more side effects then treatment with enzalutamide
alone.