Recruiting
Phase 1
Phase 2

Vasodilator Therapy

Sponsor:

Mayo Clinic

Code:

NCT07456852

Conditions

Malignant Digestive System Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Capecitabine

Diltiazem Hydrochloride

Electrocardiogram

Fluorouracil

Study Details

Brief summary:

This phase I/II trial compares the effect of drugs that causes widening of blood vessels as a result of smooth muscle relaxation (vasodilator therapy) with isosorbide mononitrate, diltiazem or placebo to reduce vasotoxicity in patients with gastrointestinal cancer receiving fluoropyrimidine therapy. Some patients develop chest pain (possibly even a heart attack, a drop in heart function, or a rhythm abnormality) during treatment with a class of cancer drugs known as fluoropyrimidines, which include 5-Fluorouracil (5-FU) and capecitabine. These side effects are believed to be due to the development of an abnormal reactivity of the blood vessels referred to as vasospasm. Vasotoxicity is damage or toxicity inflicted upon blood vessels (vascular system), often causing dysfunction, remodeling, or narrowing (vasoconstriction). It is a broad term used to describe the detrimental effects of certain agents, such as chemotherapy drugs. Researchers want to evaluate how often the reactivity of blood vessels becomes abnormal, during the treatment with 5-FU or capecitabine and how clinically relevant and controllable/preventable this phenomenon is in patients with gastrointestinal cancer.

Conditions

Malignant Digestive System Neoplasm

Study ID

NCT07456852

Start date

Apr 30, 2026

Status verified date

May, 2026

Completion date

Apr 30, 2030

Anticipated

Primary completion date

Apr 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • REGISTRATION: Age ≥ 18 years
  • REGISTRATION: Histologically or cytologically confirmed gastrointestinal malignancy (colon, rectal, gastric, esophageal, or other GI cancer) for which fluoropyrimidine therapy (5-FU or capecitabine) is indicated, either as single agent or in combination with other systemic therapy
  • REGISTRATION: Planned initiation of 5-FU (infusional) or oral capecitabine therapy, either as standard chemotherapy or as a radiosensitizer
  • REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • REGISTRATION: Ability to return to Mayo Clinic for baseline and follow-up EndoPAT testing, electrocardiogram (ECG), Holter monitoring, and blood draws
  • REGISTRATION: Provide written informed consent
  • REGISTRATION: Adequate baseline hemodynamic status: systolic blood pressure ≥ 120 mmHg and resting heart rate ≥ 70 beats/minute (to ensure safety for potential vasodilator therapy in Phase II)
  • RANDOMIZATION: Completed all phase I baseline and follow-up assessments, including EndoPAT, ECG, high-sensitivity cardiac troponin T (hs-TnT), and Holter monitoring
  • RANDOMIZATION: Demonstrated a ≥ 20% decline in reactive hyperemia index (RHI) from baseline at either phase I follow-up assessment as measured by EndoPAT
  • RANDOMIZATION: Adequate hemodynamic status prior to randomization: systolic blood pressure ≥ 120 mmHg and resting heart rate ≥ 70 beats/minute
  • RANDOMIZATION: Ability to tolerate and comply with study medication (isosorbide mononitrate, diltiazem, or placebo) per investigator assessment
  • RANDOMIZATION: Willingness to initiate study medication 5 days before and continue through the assigned fluoropyrimidine treatment cycle
  • RANDOMIZATION: Provide written informed consent for randomization phase

Exclusion Criteria:

  • REGISTRATION: Current or planned treatment with long-acting nitrates or calcium channel blockers at the time of fluoropyrimidine initiation
  • REGISTRATION: Known hypersensitivity or contraindication to nitrates or calcium channel blockers
  • REGISTRATION: Baseline systolic blood pressure < 120 mmHg or resting heart rate < 70 beats/minute
  • REGISTRATION: History of myocardial infarction ≤ 6 months prior to registration, or symptomatic heart failure \[decompensated or New York Heart Association (NYHA) III-IV\] requiring ongoing therapy
  • REGISTRATION: Recent acute coronary syndrome or coronary revascularization within 3 months of enrollment
  • REGISTRATION: High-grade atrioventricular (AV) block without pacemaker
  • REGISTRATION: Use of PDE-5 inhibitors \[e.g. sildenafil (Viagra)\] within 48 hours of enrollment
  • REGISTRATION: Uncontrolled intercurrent illness including but not limited to: unstable angina, symptomatic arrhythmias, uncontrolled infection, or psychiatric/social conditions limiting compliance with study requirements
  • REGISTRATION: Physical inability to undergo EndoPAT testing (e.g., digital amputation, severe hand deformity, or other limiting condition)
  • REGISTRATION: Pregnant or nursing persons
  • REGISTRATION: Concurrent enrollment in another interventional clinical trial that, in the opinion of the investigator, would interfere with study endpoints

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase I (EndoPAT, ECG, Holter monitoring, blood sample)

Patients undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection during their SOC 5-FU infusion (any time from 2 hours after start to end of infusion) and 12-36 hours post-infusion or SOC capecitabine infusion 5-8 days after starting cycle 1 and 5-8 days after completing cycle 1, before beginning the next cycle of treatment.

experimental: Phase II arm I (Isosorbide mononitrate)

Patients receive isosorbide mononitrate PO QD for 7-12 days on study. Patients also undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection on study.

experimental: Phase II arm II (Diltiazem hydrochloride)

Patients receive diltiazem PO QD for 7-12 days on study. Patients also undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection on study.

placebo comparator: Phase II arm III (Placebo administration)

Patients receive placebo PO QD for 7-12 days on study. Patients also undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection on study.

Interventions

Biospecimen Collection

Undergo blood sample collection

Capecitabine

Given IPO

Diltiazem Hydrochloride

Given PO

Electrocardiogram

Undergo ECG

Fluorouracil

Given IV

Holter Monitoring

Undergo Holter monitoring

Isosorbide Mononitrate

Given PO

Medical Device Usage and Evaluation

Use EndoPAT

Placebo Administration

Given PO

Questionnaire Administration

Ancillary studies

Primary outcome measure

  • Change in reactive hyperemia index (RHI) [ Time Frame: Baseline (up to 3 days before start of infusion); during infusion; 12-36 hours post-infusion ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Interventional & Ischemic Heart Disease Research Team

507-255-1724

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Interventional & Ischemic Heart Disease Research Team

507-255-1724

Principal Investigator:

Joerg Herrmann, MD

More Information

Sponsor

Mayo Clinic

Last update posted

Jun 2, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-06-02.