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Malignant Digestive System NeoplasmPhase 1/2NCT07456852

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

A Phase 1/2 study testing Biospecimen Collection, Capecitabine and Diltiazem Hydrochloride in people with Malignant Digestive System Neoplasm, run by Mayo Clinic at 1 site 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
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Digestive System Neoplasm
What is being tested?
Biospecimen Collection, Capecitabine and Diltiazem Hydrochloride
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited States
Study dates
30 Apr 2026to 30 Apr 2030
Phase
Phase 1/2
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

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

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

Clinical Trials Referral Office contact

855-776-0015

mayocliniccancerstudies@mayo.edu

Interventional & Ischemic Heart Disease Research Team contact

507-255-1724

United States1 site, 1 recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Interventional & Ischemic Heart Disease Research Team, 507-255-1724

    Recruiting

Other trials in United States

About this study

Official title: Vasotoxicity Surveillance Using EndoPAT: The VASA Pilot Study

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.

Being tested
Biospecimen Collection, Capecitabine, Diltiazem Hydrochloride, Electrocardiogram, Fluorouracil
Medical subject headings
Gastrointestinal Neoplasms

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given IPO

  • Diltiazem HydrochlorideDrug

    Also called Cardizem, Diltiazem HCl

    Given PO

  • ElectrocardiogramProcedure or surgery

    Also called ECG, EKG, Electrocardiograms

    Undergo ECG

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Holter MonitoringDevice

    Also called HOLTER CONTINUOUS ECG RECORDING, Holter Electrocardiography, Holter Monitor

    Undergo Holter monitoring

  • Isosorbide MononitrateDrug

    Also called Imdur, ISMO, Monoket, Monosordil

    Given PO

  • Medical Device Usage and EvaluationOther

    Use EndoPAT

  • Placebo AdministrationDrug

    Given PO

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT07456852
Study groupRoleWhat they receive
Phase I (EndoPAT, ECG, Holter monitoring, blood sample)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Drug: Capecitabine; Procedure: Electrocardiogram; Drug: Fluorouracil; Device: Holter Monitoring; Other: Medical Device Usage and Evaluation; Other: Questionnaire Administration
Phase II arm I (Isosorbide mononitrate)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Electrocardiogram; Device: Holter Monitoring; Drug: Isosorbide Mononitrate; Other: Medical Device Usage and Evaluation; Other: Questionnaire Administration
Phase II arm II (Diltiazem hydrochloride)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Drug: Diltiazem Hydrochloride; Procedure: Electrocardiogram; Device: Holter Monitoring; Other: Medical Device Usage and Evaluation; Other: Questionnaire Administration
Phase II arm III (Placebo administration)Placebo comparatorPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Electrocardiogram; Device: Holter Monitoring; Other: Medical Device Usage and Evaluation; Drug: Placebo Administration; Other: Questionnaire Administration

What is being measured

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

  1. Change in reactive hyperemia index (RHI)

    Will be analyzed as a continuous variable and paired t-test or Wilcoxon signed-rank test will be used depending on parametric or non-parametric distribution of RHI values. Statistical significance is set at a p-value < 0.05.

    Measured: Baseline (up to 3 days before start of infusion); during infusion; 12-36 hours post-infusion

Secondary outcomes (6)

  1. Proportion of patients with RHI decline ≥ 20%

    Assessed from baseline (prechemotherapy) to follow-up assessments during and after fluoropyrimidine exposure. Will be analyzed as a continuous variable and paired t-test or Wilcoxon signed-rank test will be used depending on parametric or non-parametric distribution of RHI values. Statistical significance is set at a p-value < 0.05.

    Measured: Up to 1 year

  2. Proportion of patients with absolute RHI ≤ 2.0

    Assessed from baseline (prechemotherapy) to follow-up assessments during and after fluoropyrimidine exposure. Will be analyzed as a continuous variable and paired t-test or Wilcoxon signed-rank test will be used depending on parametric or non-parametric distribution of RHI values. Statistical significance is set at a p-value < 0.05.

    Measured: Up to 1 year

  3. High-sensitivity troponin T (hsTnT) (indicator of myocardial ischemia)

    Will be compared between patients with and without a decline in RHI ≥20% from baseline.

    Measured: Up to 1 year

  4. Presence of Holter abnormalities (ST-segment changes, arrhythmias)

    Assessed using 48-hour continuous Holter monitoring. Will be compared between patients with and without a decline in RHI ≥20% from baseline.

    Measured: Up to 1 year

  5. Presence of ischemic symptoms (angina or angina equivalents, dyspnea, claudication)

    Will be compared between patients with and without a decline in RHI ≥20% from baseline.

    Measured: Up to 1 year

  6. Seattle Angina Questionnaire (SAQ)

    The Seattle Angina Questionnaire (SAQ) is a 19-item questionnaire used to assess self-reported health status and quality of life over the past 4 weeks in patients with coronary artery disease (CAD). Nine questions are answered on a 6-point scale (severely limited, moderately limited, somewhat limited, a little limited, not limited, limited, or did not do for other reasons). The remaining questions are answered using similar scales (e.g., not satisfied at all, mostly dissatisfied, somewhat satisfied, mostly satisfied, highly satisfied). Scores range from 0-100 with higher scores indicating better overall health (fewer symptoms).

    Measured: Baseline (up to 3 days before start of infusion); during infusion; 12-36 hours post-infusion

Timeline

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

  1. First posted9 Mar 2026
  2. Study start30 Apr 2026
  3. Primary completion30 Apr 2028 (estimated)
  4. Study completion30 Apr 2030 (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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Patients will be observed during their initial cycle of standard of care 5-FU or capecitabine treatment to establish baseline condition and evaluate for abnormal vasoreactivity prior to beginning phase II. Any patients with a \>= 20% decline in RHI from baseline as measured by EndoPAT during phase I will undergo randomization and continue to phase II.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07456852
Sponsor's protocol ID
MC250411
Other IDs
NCI-2026-01065, MC250411, 25-011528
Status last verified
May 2026
First submitted
2 Mar 2026
Last updated
2 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biospecimen Collection, Capecitabine and Diltiazem Hydrochloride in people with Malignant Digestive System Neoplasm, run by Mayo Clinic at 1 site 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 13 inclusion and 11 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 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Contact Clinical Trials Referral Office (855-776-0015, mayocliniccancerstudies@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). 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 NCT07456852.

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 2 Jun 2026.

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