Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer

Summary

This phase I trial tests the safety, best dose, and effectiveness of ZEN003694 in combination with cetuximab and encorafenib in treating patients with colorectal cancer that has not responded to previous treatment (refractory), that has come back after a period of improvement (relapsed), and that has spread from where it first started (primary site) to other places in the body (metastatic). ZEN003694 is a protein inhibitor that binds to BET proteins. When ZEN003694 binds to BET proteins, it disrupts gene expression. Preventing the expression of certain growth-promoting genes may inhibit proliferation of tumor cells that over-express BET proteins. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Encorafenib is an enzyme inhibitor. It inhibits pathways that are responsible for controlling cell proliferation and survival, which may lead to a decrease in tumor cell proliferation. Both cetuximab and encorafenib have been approved to treat cancer. Adding ZEN003694 to cetuximab and encorafenib may be more effective at treating patients with refractory metastatic colorectal cancer than giving the usual treatment (cetuximab and encorafenib) alone.

Conditions

• Metastatic Colorectal Adenocarcinoma
• Recurrent Colorectal Adenocarcinoma
• Refractory Colorectal Adenocarcinoma
• Stage IV Colorectal Cancer AJCC v8

Interventions

DRUG

BET Bromodomain Inhibitor ZEN-3694

Given PO

PROCEDURE

Biopsy Procedure

Undergo biopsy

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

BIOLOGICAL

Cetuximab

Given IV

PROCEDURE

Computed Tomography

Undergo CT

PROCEDURE

Echocardiography Test

Undergo ECHO

DRUG

Encorafenib

Given PO

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Salvador Alonso Martinez · University of Texas MD Anderson Cancer Center LAO

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-06-05

Primary Completion

2027-01-30

Completion

2027-01-30

FDA Drug

Yes

Countries

• United States

Study Locations