National Cancer Institute (NCI)
This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with cisplatin and etoposide or carboplatin and paclitaxel in treating patients with NUT carcinoma. Another purpose of this study is to see whether there are any changes in patient's tumor or blood characteristics (e.g. genes, molecules, etc.) due to combination therapy. ZEN003694 inhibits the production of certain growth-promoting proteins and may prevent proliferation of tumor cells that use those proteins for their growth. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Combination therapy with ZEN003694 and etoposide and cisplatin or carboplatin and paclitaxel may be safe and effective in treating patients with NUT carcinoma.
PRIMARY OBJECTIVE: I. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the addition of BET bromodomain inhibitor ZEN-3694 (ZEN003694) to etoposide and cisplatin (EP) in participants with NUT carcinoma (NC). SECONDARY OBJECTIVES: I. Evaluate the preliminary progression-free survival (PFS) rate, overall response rate (ORR), duration of response (DoR), and overall survival (OS) of the addition of ZEN003694 to etoposide and cisplatin (EP) in participants with NC utilizing Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. II. Determine…
Inclusion Criteria: * PHASE 1, CARBOPLATIN/PACLITAXEL SAFETY COHORT, \& NON-THORACIC, NON-BRD4 EXPLORATORY COHORT: Participants must have a diagnosis of NC based on standard criteria for the disease, with diagnostic testing performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory: * Ectopic expression of NUT protein per World Health Organization (WHO) criteria (World Health Organization \[WHO\], 2021) as determined by immunohistochemistry (IHC) testing, OR * Detection of the NUT gene translocation as determined by fluorescence in situ hybridization (FISH) testing, O…
Given PO
Undergo biopsy
Undergo blood sample collection
Given IV
Given IV
Given IV
Undergo imaging scans
Given IV