PRIMARY OBJECTIVE:~I. To determine the safety and tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of BET bromodomain inhibitor ZEN-3694 (ZEN003694 [ZEN-3694]) in combination with capecitabine in patients with solid tumors.~SECONDARY OBJECTIVES:~I. To observe and record anti-tumor activity of ZEN003694 (ZEN-3694) in combination with capecitabine.~II. To determine the pharmacokinetics (PK) of ZEN003694 (ZEN-3694) in combination with capecitabine.~III. To determine the pharmacodynamics (PD) of ZEN003694 (ZEN-3694) in combination with capecitabine (death receptor 5 [DR5] dynamics and apoptosis).~IV. To identify molecular subpopulations particularly sensitized to bromodomain and extra-terminal motif inhibitor (BETi) and capecitabine.~OUTLINE: This is a dose-escalation study of ZEN003694 and capecitabine, followed by a dose-expansion study.~Patients receive ZEN003694 orally (PO) and capecitabine PO on study. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, and collection of blood samples throughout the trial. Patients may also undergo biopsies during screening and on study.
This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with capecitabine in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). ZEN003694 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as capecitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ZEN003694 in combination with capecitabine may help shrink cancer better than the usual approach alone.