Vasodilator Therapy for Gastrointestinal Cancer

CT
Overseen ByClinical Trials Referral Office

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

JH

Joerg Herrmann, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Inclusion Criteria

I am able to care for myself and do daily activities.
* 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
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I

Patients undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection during their SOC 5-FU 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

1-2 weeks
Multiple visits for monitoring and sample collection

Phase II

Patients receive isosorbide mononitrate, diltiazem, or 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

7-12 days
Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of RHI and other secondary outcomes

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

  • Diltiazem Hydrochloride
  • Isosorbide Mononitrate

How Is the Trial Designed?

4

Treatment groups

Experimental Treatment

Placebo Group

Group I: Phase II arm II (Diltiazem hydrochloride)Experimental Treatment6 Interventions
Group II: Phase II arm I (Isosorbide mononitrate)Experimental Treatment6 Interventions
Group III: Phase I (EndoPAT, ECG, Holter monitoring, blood sample)Experimental Treatment7 Interventions
Group IV: Phase II arm III (Placebo administration)Placebo Group6 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials
3,427
Recruited
3,221,000+