NCT05803382

Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers

Phase I Trial of ZEN003694 (ZEN-3694) in Combination With Capecitabine in Patients With Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with the usual treatment 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) and that it has progressed on previous standard treatment. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Capecitabine is in a class of medications called antimetabolites. It is taken up by cancer cells and breaks down into fluorouracil, a substance that kills cancer cells. Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors.

Detailed description

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) once daily (QD) and capecitabine PO twice daily (BID) 2 weeks on, 1 week off during each treatment cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 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 while on the study. After completion of study treatment, patients are followed up for safety 30 days after the last dose, and then every 3 months for 12 months.

Conditions

• Metastatic Colorectal Carcinoma
• Metastatic Malignant Solid Neoplasm
• Stage IV Colorectal Cancer AJCC v8
• Unresectable Colorectal Carcinoma
• Unresectable Malignant Solid Neoplasm

Interventions

Type	Name	Description
DRUG	BET Bromodomain Inhibitor ZEN-3694	Given PO
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
DRUG	Capecitabine	Given PO
PROCEDURE	Computed Tomography	Undergo CT and PET/CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

• Start date: 2023-11-08
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2023-04-07
• Last updated: 2026-04-13

Locations

22 sites across 1 country: United States

Regulatory

• FDA-regulated drug study