60 Participants NeededMy employer runs this trial

Vasodilator Therapy for Gastrointestinal Cancer

CT
I&
Overseen ByInterventional & Ischemic Heart Disease Research Team

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether drugs that widen blood vessels, such as isosorbide mononitrate and diltiazem (a vasodilator), can reduce heart-related side effects in patients with gastrointestinal cancer receiving fluoropyrimidine chemotherapy. These side effects, including chest pain or heart attacks, may result from excessive narrowing of blood vessels (vasospasm). Participants may qualify if they have gastrointestinal cancer, are beginning treatment with 5-FU or capecitabine, and have experienced significant changes in blood vessel reactivity. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works and measure its effectiveness in an initial group, offering participants a chance to contribute to important medical advancements.

Do I need to stop my current medications for the trial?

You may need to stop taking long-acting nitrates or calcium channel blockers, as the trial excludes those currently or planning to use these medications. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that isosorbide mononitrate is usually well-tolerated, with few major side effects when used for conditions like heart disease. It primarily prevents chest pain, suggesting potential safety for individuals with gastrointestinal cancer.

Research also indicates that diltiazem is well-tolerated. It often treats high blood pressure and chest pain, with most side effects being mild, such as dizziness or tiredness.

Both treatments have been used safely for other conditions, suggesting they might be safe options in this trial to help reduce blood vessel damage during cancer treatment.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore new ways to tackle gastrointestinal cancer using vasodilators, like Diltiazem Hydrochloride and Isosorbide Mononitrate. These drugs work by widening blood vessels, potentially improving blood flow to tumors, which might enhance the effectiveness of existing treatments like chemotherapy. Unlike traditional treatments that directly target cancer cells, these vasodilators could improve how other therapies are delivered or absorbed in the body. This approach might lead to better outcomes and possibly fewer side effects, providing a fresh angle in the fight against this type of cancer.

What evidence suggests that this trial's treatments could be effective for gastrointestinal cancer?

Research has shown that isosorbide mononitrate, which participants in this trial may receive, can improve blood vessel function. It has effectively helped certain cancer treatments accumulate in tumors, potentially enhancing their effectiveness. Studies also suggest that isosorbide mononitrate can work well with other medicines to slow cancer cell growth.

For diltiazem, another treatment option in this trial, research found that it can enhance the effectiveness of chemotherapy drugs like 5-Fluorouracil (5-FU) in killing cancer cells. It is considered a promising option to improve cancer treatment efficacy. These findings suggest that both treatments might help manage blood vessel issues in patients receiving chemotherapy for gastrointestinal cancer.24678

Who Is on the Research Team?

JH

Joerg Herrmann, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults (18+) with confirmed gastrointestinal cancer who are about to start treatment with 5-FU or capecitabine. Participants must be able to visit Mayo Clinic for tests, have good heart function and blood pressure, and show certain changes in blood vessel reactivity during initial assessments.

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
See 7 more

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

Trial Overview

The study compares two drugs that widen blood vessels—isosorbide mononitrate and diltiazem—to a placebo. All participants receive standard chemotherapy (5-FU or capecitabine). The goal is to see if these drugs can prevent damage to blood vessels caused by the cancer treatment.

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+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33011221/

Diltiazem potentiates the cytotoxicity of gemcitabine and 5 ...

Our findings suggest that diltiazem may be potential neoadjuvant therapy to enhance the response of PC to gemcitabine or 5-FU treatment.

Diltiazem potentiates the cytotoxicity of gemcitabine and 5- ...

Significance Our findings suggest that diltiazem may be potential neoadjuvant therapy to enhance the response of PC to gemcitabine or 5-FU treatment.

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/8521739/

Diltiazem potentiation of doxorubicin cytotoxicity and ...

However, pretreatment with diltiazem increased survival to 70% with a mean survival time of 43 days. Diltiazem treatment increased the intracellular level of ...

Vasodilator Therapy for Gastrointestinal Cancer

This phase I/II trial compares the effect of drugs that causes widening of blood vessels as a result of smooth muscle relaxation ...

The efficacy of diltiazem, glyceryl trinitrate, nifedipine, .. ...

The primary outcome was AF healing, with secondary outcomes including recurrence rates, pain reduction (visual analog scale), and adverse ...

Diltiazem inhibits breast cancer metastasis via mediating ...

These findings suggest that diltiazem regulates EMT and cell motility through elevating GDF-15 expression in breast cancers in vitro and in vivo.

Controlled Release Technologies for Diltiazem Hydrochloride

Moreover, DH has a relatively short elimination half-life (approximately 3–4.5 h), requiring multiple daily doses to maintain therapeutic plasma ...

Bleeding Risk With Oral Anticoagulants and Verapamil or ...

Findings In this comparative effectiveness study using data from 48 442 patients, rates of bleeding were increased for patients receiving ...