Vasodilator Therapy With Isosorbide Mononitrate or Diltiazem to Reduce Vasotoxicity in Patients With Gastrointestinal Cancer Receiving Fluoropyrimidine Therapy

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

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

DRUG

Capecitabine

Given IPO

DRUG

Diltiazem Hydrochloride

Given PO

PROCEDURE

Electrocardiogram

Undergo ECG

DRUG

Fluorouracil

Given IV

DEVICE

Holter Monitoring

Undergo Holter monitoring

DRUG

Isosorbide Mononitrate

Given PO

OTHER

Medical Device Usage and Evaluation

Use EndoPAT

DRUG

Placebo Administration

Given PO

OTHER

Questionnaire Administration

Ancillary studies

Sponsors & Collaborators

• Mayo Clinic

  lead OTHER

Principal Investigators

• Joerg Herrmann, MD · Mayo Clinic in Rochester

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-31

Primary Completion

2028-03-31

Completion

2030-03-31

FDA Drug

Yes

Countries

• United States

Study Locations