Intensive Blood Pressure Control for Cardiotoxicity in Cancer Patients

Recruiting at 6 trial locations

Overseen By Jennifer Liu, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Cardiac comorbidity, Stroke, Renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 months

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether aggressively managing blood pressure during breast cancer treatment can reduce heart-related side effects of cancer therapy. Researchers compare two strategies: a standard approach and a more intensive method to maintain low blood pressure. Women with breast cancer who have high blood pressure and are undergoing specific chemotherapy treatments may qualify for this study. Participants will receive either standard or higher doses of blood pressure medication, along with lifestyle tips to manage hypertension. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on blood pressure treatment strategies rather than specific medications.

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

Research has shown that closely managing blood pressure can be safe for cancer patients, but it requires careful attention. Studies have found that controlling blood pressure can lower the risk of heart problems in cancer survivors. Although this method is generally safe, cancer treatments can often alter blood pressure levels.

Previous studies reported moderate to severe high blood pressure during cancer treatments. Moderate cases occur in about 90 out of 100 people per year, while severe cases occur in about 40 out of 100 people per year. Thus, while closely managing blood pressure is promising, it must be done with caution, especially for cancer patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a more intensive approach to controlling high blood pressure in cancer patients, which could significantly reduce heart-related side effects from cancer treatments. Unlike standard treatments targeting a systolic blood pressure (SBP) of less than 140 mm Hg, this trial aims for a more aggressive SBP target of less than 120 mm Hg. This approach could potentially offer better protection against the cardiotoxic effects of cancer therapies, improving overall patient outcomes. Additionally, all participants receive comprehensive lifestyle and dietary guidance, which complements the medication regimen and may enhance blood pressure control compared to medication alone.

What evidence suggests that this trial's treatments could be effective for cardiotoxicity in cancer patients?

Research has shown that closely managing blood pressure can greatly reduce the risk of serious heart issues. In this trial, participants will be randomized into different treatment arms to compare the effects of standard-of-care antihypertensive medications with higher dose antihypertensive medications. The SPRINT study found that maintaining a lower blood pressure effectively reduced heart problems for cancer survivors. Participants aimed to keep their systolic blood pressure below 120, which proved more effective than the usual goal of below 140. Although these studies did not focus solely on cancer patients, they suggest that stricter blood pressure control might help lessen heart-related side effects during cancer treatment. This is important because many cancer treatments can affect the heart. ^{1 2 3 5 6}

Who Is on the Research Team?

Anthony Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women diagnosed with breast cancer (stages I-IV) who are about to undergo treatment that could harm the heart and have high blood pressure (≥130 mm Hg). They must be able to follow the study's rules, use a Bluetooth-enabled mobile device, and if participating in exercise testing, complete a baseline test without certain heart risks. Excluded are those with severe kidney issues, measurement difficulties due to arm size or lymphedema, recent serious heart problems or stroke.

Inclusion Criteria

Willing and able to comply with the requirements of the protocol.

Your blood pressure is higher than 130 mm Hg.

Participant must have and be willing to use their bluetooth enabled wifi or cellular mobile device

Exclusion Criteria

I cannot have my blood pressure measured accurately on either arm.

Your arm is too big for the blood pressure cuff to get an accurate reading.

I have had recent serious heart problems or a stroke.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard or intensive antihypertensive treatment, with medication titration every 4 weeks for the first 3 months, then every 3 months for a total of 12 months

12 months

Visits every 4 weeks for the first 3 months, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intensive Approach to Treating High Blood Pressure

Trial Overview

The PROTECT trial is examining whether intensively treating high blood pressure during breast cancer therapy can better lower blood pressure and reduce heart damage risk compared to standard treatment. It's not testing specific drugs but rather strategies for setting systolic blood pressure goals.

How Is the Trial Designed?

Group I: standard-of-care antihypertensive medications Experimental Treatment 6 Interventions

SBP control will consist of treatment with antihypertensive medications titrated every 4 weeks for the first 3 months, and then every 3 months in months 4-12. SBP control will be achieved by titration of antihypertensive medications based upon a standardized algorithm and will be implemented during a 12-month study period. At the time of randomization, no antihypertensive treatments may be initiated or modified if SBP is ≥160 mm Hg. The clinical context may be considered at each visit to inform decision-making regarding treatment initiation or modification, at the discretion of the treating provider.

Group II: higher dose antihypertensive medications Experimental Treatment 6 Interventions

Patients randomized to intensive SBP control will be treated to achieve an SBP goal \<120 mm Hg, and patients randomized to standard SBP control will be treated to achieve an SBP goal \<140 mm Hg. Antihypertensive medications will be titrated on the basis of seated blood pressure measurements obtained after a 5-min rest period. All participants will be provided with dietary (e.g., 1500mg/d sodium restriction) and lifestyle recommendations as background therapy for optimizing HTN control.The clinical context may be considered at each visit to inform decision-making regarding treatment initiation or modification, at the discretion of the treating provider.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Combination therapy is often necessary for hypertensive patients to achieve blood pressure targets, especially when monotherapy is insufficient, and it can provide enhanced efficacy and reduced side effects due to lower doses.

The fixed combination of olmesartan medoxomil and hydrochlorothiazide has been approved for hypertension treatment, leveraging the benefits of both an angiotensin receptor blocker and a diuretic to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olmesartan medoxomil plus hydrochlorothiazide for treating hypertension. Barrios, V., Escobar, C.[2015]

In a study of 7448 heart failure patients, those with systolic blood pressure (SBP) at discharge below 120 mm Hg had a significantly decreased long-term survival, particularly in patients with a left ventricular ejection fraction of 40% or less.

The relationship between discharge SBP and mortality followed a U-shaped curve, indicating that both low (<100 mm Hg) and high (>140 mm Hg) SBP values were associated with shorter survival times, highlighting the importance of maintaining optimal blood pressure levels at discharge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of blood pressure at hospital discharge with mortality in patients diagnosed with heart failure. Lee, DS., Ghosh, N., Floras, JS., et al.[2010]

Cancer patients and survivors face a higher risk of cardiovascular disease, particularly hypertension, which is exacerbated by chemotherapy treatments that affect blood vessel function and kidney health.

Effective management of hypertension in cancer patients requires careful blood pressure monitoring, considering factors like other treatments and pain, and selecting antihypertensive medications that address specific health issues related to cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertension in Cancer Patients and Survivors: Epidemiology, Diagnosis, and Management. Cohen, JB., Geara, AS., Hogan, JJ., et al.[2023]

Uncontrolled arterial hypertension (AH) significantly increases the risk of cardiotoxicity in cancer patients undergoing treatment, especially when there is existing heart-related organ damage (HMOD).

Effective management of AH and HMOD is crucial for improving the clinical outcomes of oncologic patients, as neglecting cardiovascular health can compromise the success of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Arterial Hypertension and Hypertension-Mediated Organ Damage in Cardiotoxicity of Anticancer Therapies. Tini, G., Tocci, G., Battistoni, A., et al.[2023]

Hypertension is a common issue in cancer patients, often exacerbated by certain oncology drugs, particularly new tyrosine kinase inhibitors, which can lead to serious complications if not managed properly.

Effective management of hypertension in cancer patients involves using standard antihypertensive medications and requires careful cardiac monitoring throughout treatment to ensure both immediate and long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypertension and cancer : Dangerous Liaisons]. Duvillier, P.[2022]

Hypertension is linked to a higher risk of developing certain cancers and can worsen cancer-related mortality, highlighting the importance of managing blood pressure in cancer patients.

Certain cancer therapies, such as VEGF inhibitors and tyrosine kinase inhibitors, can induce or worsen hypertension, necessitating careful blood pressure management to prevent cardiotoxicity and long-term cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etiology and management of hypertension in patients with cancer. Mohammed, T., Singh, M., Tiu, JG., et al.[2021]

Angiotensin II-induced hypertension chemotherapy using cis-diamminedichloroplatinum (DDP) or carboquone (CQ) was found to be more effective than conventional chemotherapy alone in treating mouse mammary carcinoma, indicating a potential benefit in using hypertension as a therapeutic strategy.

The modified hypertension chemotherapy, which combined DDP with cardiotonics like aminophylline or trans-pi-oxocamphor, improved antitumor effects without increasing general toxicity, suggesting that this approach enhances drug delivery to tumors rather than increasing the drug's cytotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Improvement of cancer therapy by angiotensin II-induced hypertension chemotherapy]. Baba, T., Taniguchi, S.[2013]

In a study of 10,802 hypertensive patients with heart failure, nearly half (48.1%) had systolic blood pressure levels of 130 mm Hg or higher, indicating a significant challenge in achieving recommended blood pressure control.

Factors such as race-ethnicity, gender, insurance status, and having a primary care physician were associated with higher systolic blood pressure levels, highlighting the need for targeted interventions to improve treatment and health equity in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Pressure Control in a Diverse Population of Hypertensive Patients With Heart Failure. Nguyen, HM., Mahabaleshwarkar, R., Nandkeolyar, S., et al.[2023]

Hypertensive cardiotoxicity, which can occur in 33-68% of cancer patients undergoing treatment, is a significant side effect of both conventional and novel cancer therapies, highlighting the need for careful monitoring of blood pressure during treatment.

Interestingly, while hypertension is a common side effect, it can also indicate a positive response to cancer treatment, creating a paradox where managing hypertension is crucial yet may also reflect treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertensive Cardiotoxicity in Cancer Treatment-Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies-Epidemiology, Incidence, and Pathophysiology. Chung, R., Tyebally, S., Chen, D., et al.[2020]

Despite the proven effectiveness of antihypertensive therapy, many patients do not achieve their target blood pressure, indicating a need for improved treatment strategies.

Enhancing blood pressure control through better patient assessment, caregiver support, and specialist referrals could significantly benefit patients, especially those with resistant hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guest Editorial Challenges in Resistant Hypertension. Kahan, T.[2023]

Most hypertensive patients require combination drug therapy for effective blood pressure control, with fixed combination drugs being preferred to improve patient compliance and minimize side effects.

Current blood pressure targets are set at 135/80 mm Hg for essential hypertension and 120/70 mm Hg for patients with diabetes or renal diseases, with ACE inhibitors or angiotensin II blockers recommended for those with renal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Goal blood pressure values from the nephrologic viewpoint]. Hörl, WH.[2007]

In a study of 143 cancer patients with elevated blood pressure, over half had controlled cancer but more than a third were not receiving treatment, indicating a potential opportunity for hypertension management in this group.

Only 9% of patients received specific discharge instructions for hypertension follow-up, highlighting a gap in care that could be addressed in emergency settings to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertension in cancer patients seeking acute care: an opportunity to intervene. Escalante, CP., Weiser, MA., Lam, T., et al.[2019]

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The purpose of this study to find out whether an intensive approach to treating high blood pressure during breast cancer treatment is safe and more effective

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Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction.

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This trial demonstrated that cardiovascular outcomes in high risk patients were improved with intensive blood pressure control. The ...