Recruiting
Phase 1

ZEN003694 with Capecitabine

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05803382

Conditions

Metastatic Colorectal Carcinoma

Metastatic Malignant Solid Neoplasm

Stage IV Colorectal Cancer AJCC v8

Unresectable Colorectal Carcinoma

Unresectable Malignant Solid Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BET Bromodomain Inhibitor ZEN-3694

Biopsy Procedure

Biospecimen Collection

Capecitabine

Computed Tomography

Study Details

Brief 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.

Conditions

Metastatic Colorectal Carcinoma

Metastatic Malignant Solid Neoplasm

Stage IV Colorectal Cancer AJCC v8

Unresectable Colorectal Carcinoma

Unresectable Malignant Solid Neoplasm

Study ID

NCT05803382

Start date

Nov 8, 2023

Status verified date

Jun, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Dose Escalation additional criteria: Patients must have histologically confirmed cancer that is metastatic or unresectable and must have progressed on standard therapies which would have included fluorouracil (5-FU) or capecitabine
  • Dose Escalation additional criteria specifically for colorectal cancer (CRC) patients: Willingness and ability to undergo a pre-treatment biopsy
  • Dose Expansion additional criteria: Patients must have histologically confirmed CRC that is metastatic or unresectable and must have progressed on standard therapies which would have included 5-FU or capecitabine
  • Dose Expansion additional criteria: Willingness and ability to undergo pre- and on- treatment biopsies
  • Patients must have measurable disease
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with capecitabine in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky >= 60%)
  • Availability of archival tumor tissue at the time of patient enrollment for molecular profiling studies
  • Prior to study dosing, previous systemic therapy must have been completed for at least five half-lives or 2 weeks, whichever is shorter
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 3 x institutional ULN
  • Glomerular filtration rate (GFR) >= 50 mL/min/1.73 m\^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients should be New York Heart Association Functional Classification of class 2B or better
  • The effects of ZEN003694 (ZEN-3694) and capecitabine on the developing human fetus are unknown. For this reason and because BET inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential and men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694) and capecitabine administration
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

  • Previous treatment with BET inhibitors
  • History of inability to tolerate capecitabine at the projected treatment dose on this trial
  • Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed
  • Treatment for HIV, hepatitis B or hepatitis C only if this interferes with the current treatment (e.g. through drug-drug interactions)
  • Gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication
  • Hepatic tumor burden > 30% or peritoneal carcinomatosis
  • Untreated/uncontrolled central nervous system (CNS) disease
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Severe intercurrent illness or comorbidity
  • Inability to comply with the protocol and/or not willing or who will not be available for follow-up assessments
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy up to and including grade 2
  • Patients who are receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or other agents used in study
  • Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors of CYP3A4 must be discontinued at least 7 days, and inducers 14 days prior to the first dose of ZEN003694 and capecitabine. Substrates of CYP1A2 with narrow therapeutic window must be avoided while taking ZEN003694
  • Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694). These potential risks may also apply to other agents used in this study

Study Design

Enrollment

30 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (ZEN003694, capecitabine)

Patients receive ZEN003694 PO QD and capecitabine PO 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 CT or MRI, PET/CT, and collection of blood samples throughout the trial. Patients may also undergo biopsies during screening and while on the study.

Interventions

BET Bromodomain Inhibitor ZEN-3694

Given PO

Biopsy Procedure

Undergo biopsy

Biospecimen Collection

Undergo collection of blood samples

Capecitabine

Given PO

Computed Tomography

Undergo CT and PET/CT

Magnetic Resonance Imaging

Undergo MRI

Positron Emission Tomography

Undergo PET/CT

Primary outcome measure

  • Incidence of adverse events [ Time Frame: Up to 30 days after last dose ]
  • Maximum tolerated dose (MTD) [ Time Frame: During the first cycle of therapy (Cycles = 21 days) ]
  • Recommended phase 2 dose (RP2D) [ Time Frame: Up to 30 days after last dose ]

Central Contacts and Locations

Locations

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Fa-Chyi Lee

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Fa-Chyi Lee

UF Health Cancer Institute - Gainesville

Recruiting

Gainesville, Florida, United States, 32610

Contacts

Site Public Contact

352-273-8010cancer-center@ufl.edu

Principal Investigator:

Thomas J. George

University of Kansas Clinical Research Center

Recruiting

Fairway, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Joaquina C. Baranda

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Joaquina C. Baranda

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Joaquina C. Baranda

Montefiore Medical Center-Einstein Campus

Recruiting

The Bronx, New York, United States, 10461

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Chaoyuan Kuang

Montefiore Medical Center-Weiler Hospital

Recruiting

The Bronx, New York, United States, 10461

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Chaoyuan Kuang

Montefiore Medical Center - Moses Campus

Recruiting

The Bronx, New York, United States, 10467

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Chaoyuan Kuang

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Davendra P. Sohal

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Davendra P. Sohal

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

Susanna V. Ulahannan

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Anwaar Saeed

Vanderbilt Breast Center at One Hundred Oaks

Recruiting

Nashville, Tennessee, United States, 37204

Contacts

Site Public Contact

800-811-8480

Principal Investigator:

Thatcher R. Heumann

Vanderbilt University/Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Site Public Contact

800-811-8480

Principal Investigator:

Thatcher R. Heumann

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 31, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-31.