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NCT05803382 | RECRUITING | Metastatic Colorectal Carcinoma

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

National Cancer Institute (NCI)

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.

Condition or disease

Metastatic Colorectal Carcinoma

Metastatic Malignant Solid Neoplasm

Stage IV Coloresectal Cancer Ajcc v8

Unresectable Colorectal Carcinoma

Unresectable Malignant Solid Neoplasm

Intervention/treatment

BET Bromodomain Inhibitor ZEN-3694

Biopsy Procedure

Biospecimen Collection

Capecitabine

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Phase

PHASE1

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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 30 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : Phase I Trial of ZEN003694 (ZEN-3694) in Combination With Capecitabine in Patients With Solid Tumors
Actual Study Start Date : 2023-11-08
Estimated Primary Completion Date : 2026-06-30
Estimated Study Completion Date : 2026-06-30

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
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
Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers

Location Details

NCT05803382

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, California

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

RECRUITING

United States, Florida

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States, 32610

RECRUITING

United States, Illinois

Memorial Hospital East

Shiloh, Illinois, United States, 62269

RECRUITING

United States, Kansas

University of Kansas Clinical Research Center

Fairway, Kansas, United States, 66205

RECRUITING

United States, Kansas

University of Kansas Cancer Center

Kansas City, Kansas, United States, 66160

RECRUITING

United States, Kansas

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States, 66205

RECRUITING

United States, Missouri

Siteman Cancer Center at West County Hospital

Shrimp, Missouri, United States, 63141

RECRUITING

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

RECRUITING

United States, Missouri

Siteman Cancer Center-South County

Saint Louis, Missouri, United States, 63129

RECRUITING

United States, Missouri

Siteman Cancer Center at Christian Hospital

Saint Louis, Missouri, United States, 63136

RECRUITING

United States, Missouri

Siteman Cancer Center at Saint Peters Hospital

Saint Peters, Missouri, United States, 63376

RECRUITING

United States, New York

Montefiore Medical Center-Einstein Campus

Bronx, New York, United States, 10461

RECRUITING

United States, New York

Montefiore Medical Center-Weiler Hospital

Bronx, New York, United States, 10461

RECRUITING

United States, New York

Montefiore Medical Center - Moses Campus

Bronx, New York, United States, 10467

RECRUITING

United States, New York

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

New York, New York, United States, 10032

RECRUITING

United States, Ohio

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, United States, 45219

RECRUITING

United States, Ohio

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, United States, 45069

RECRUITING

United States, Oklahola

University of Oklahoma Health Sciences Center

Ololama City, Okholohan, United States, 73104

RECRUITING

United States, Pennsylvania

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States, 15232

RECRUITING

United States, Pennsylvania

UPMC Hillman Cancer Center LAO

Pittsburgh, Pennsylvania, United States, 15232

RECRUITING

United States, Tennessee

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, United States, 37204

RECRUITING

United States, Tennessee

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States, 37232