AzTrials
AzTrials

Metastatic Colorectal CarcinomaPhase 1NCT05803382

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

A Phase 1 study testing BET Bromodomain Inhibitor ZEN-3694, Biopsy Procedure and Biospecimen Collection in people with Metastatic Colorectal Carcinoma and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 22 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BET Bromodomain Inhibitor ZEN-3694, Biopsy Procedure and Biospecimen Collection
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
22 sitesUnited States
Study dates
8 Nov 2023to 30 Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 22Show fewer
  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

22 sites in 1 country. Contact the study team or a site near you to ask about taking part.

22 sites in 1 country

United States22 sites, 16 recruiting

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

    Site Public Contact, 513-584-7698, cancer@uchealth.com

    Davendra P. Sohal

    Recruiting

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

    Active, not recruiting

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

    Active, not recruiting

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Joaquina C. Baranda

    Recruiting

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

    Site Public Contact, 352-273-8010, cancer-center@ufl.edu

    Thomas J. George

    Recruiting

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Fa-Chyi Lee

    Recruiting

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Joaquina C. Baranda

    Recruiting

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

    Site Public Contact, 800-811-8480

    Thatcher R. Heumann

    Recruiting

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

    Site Public Contact, 800-811-8480

    Thatcher R. Heumann

    Recruiting

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

    Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Ryan Moy

    Recruiting

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

    Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu

    Susanna V. Ulahannan

    Recruiting

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Fa-Chyi Lee

    Recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Site Public Contact, 412-647-8073

    Anwaar Saeed

    Recruiting

  • Memorial Hospital East

    Shiloh, Illinois, 62269

    Active, not recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Active, not recruiting

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

    Active, not recruiting

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

    Active, not recruiting

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Chaoyuan Kuang

    Recruiting

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Chaoyuan Kuang

    Recruiting

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Chaoyuan Kuang

    Recruiting

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

    Site Public Contact, 513-584-7698, cancer@uchealth.com

    Davendra P. Sohal

    Recruiting

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Joaquina C. Baranda

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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. NOTE: Patients do not receive ZEN003694 on day 1 of cycle 1. 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.

Being tested
BET Bromodomain Inhibitor ZEN-3694, Biopsy Procedure, Biospecimen Collection, Capecitabine, Computed Tomography
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BET Bromodomain Inhibitor ZEN-3694Drug

    Also called BETi ZEN-3694, ZEN 3694, ZEN-3694, ZEN003694

    Given PO

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT and PET/CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

Study groups in NCT05803382
Study groupRoleWhat they receive
Treatment (ZEN003694, capecitabine)ExperimentalPatients 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. NOTE: Patients do not receive ZEN003694 on day 1 of cycle 1. 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.
Receives: Drug: BET Bromodomain Inhibitor ZEN-3694; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Capecitabine; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Adverse events and serious adverse events will be tabulated for each dose levels. As per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

    Measured: Up to 30 days after last dose

  2. Maximum tolerated dose (MTD)

    Defined as the highest dose level with no more than 1/6 dose-limiting toxicity. Dose level 4 was selected as the MTD.

    Measured: During the first cycle of therapy (Cycles = 21 days)

  3. Recommended phase 2 dose (RP2D)

    Dose level 4 was selected as the RP2D.

    Measured: Up to 30 days after last dose

Secondary outcomes (6)

  1. Anti-tumor activity of ZEN003694 (ZEN-3694) in combination with capecitabine

    Treatment response will be assessed for all patients based on Response Evaluation Criteria in Solid Tumors version 1.1: complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD). Clinical benefit rate is defined as the addition of CR, PR and SD.

    Measured: Up to 12 months

  2. Progression free survival (PFS)

    PFS will be estimated by the Kaplan-Meier method, along with 95% confidence regions.

    Measured: Up to 12 months

  3. Objective response rate (ORR)

    Defined as the addition of CR and PR. The probability of ORR and clinical benefit rate will be estimated with exact 95% binomial confidence intervals.

    Measured: Up to 12 months

  4. Pharmacokinetics (PK) of ZEN003694 (ZEN-3694) in combination with capecitabine

    Will determine the PK of ZEN003694 (ZEN-3694) in combination with capecitabine. Capecitabine PK will be evaluated in the absence and presence of ZEN003694 (ZEN-3694) and Cmax and area under curve (AUC) will be compared with a paired test. ZEN003694 (ZEN-3694) PK will be evaluated in the presence of capecitabine and Cmax and AUC will be compared descriptively with historical data.

    Measured: Up to 12 months

  5. Pharmacodynamics (PD) of ZEN003694 (ZEN-3694) in combination with capecitabine

    Will determine PD of ZEN003694 (ZEN-3694) in combination with capecitabine. Ribonucleic acid sequencing of death receptor 5 (DR5). DR5 is expected to be increased by the combination ZEN003694 (ZEN-3694) in combination with capecitabine. Pre-post comparisons will be made within patients enrolled on the expansion cohort using a non-parametric paired test, at a significance level (alpha) of 0.05. Apoptosis by Pharmacodynamic Assay Development and Implementation Section (PADIS) lab. Panel 3 is priority, but other panels will be evaluated with remaining lysate. Apoptosis is expected to be increased by the combination ZEN003694 (ZEN-3694) in combination with capecitabine. Pre-post comparisons will be made within patients enrolled on the expansion cohort using a non-parametric paired test, at a significance level (alpha) of 0.05.

    Measured: Up to 12 months

  6. Molecular subpopulations particularly sensitized to BETi and capecitabine

    Will identify molecular subpopulations particularly sensitized to BETi and capecitabine. Based on WES of archival tissue, we will evaluate descriptively any mutations in genes relevant to DNA damage repair, signaling and (fluoropyrimidine) metabolism, any relations with peculiar response and/or toxicity.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2023
  2. Study start8 Nov 2023
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion30 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05803382
Sponsor's protocol ID
NCI-2023-02652
Other IDs
NCI-2023-02652, HCC 23-096, 10579, 10579, UM1CA186690
Status last verified
Sep 2026
First submitted
6 Apr 2023
Last updated
28 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BET Bromodomain Inhibitor ZEN-3694, Biopsy Procedure and Biospecimen Collection in people with Metastatic Colorectal Carcinoma and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 30 days after last dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05803382.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in