A Study of Blood Pressure Control During Cancer Treatment

Intensive Blood Pressure Control During Cardiotoxic Breast Cancer Treatment (PROTECT), A Randomized Controlled Trial

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 than standard blood pressure treatment at lowering blood pressure levels and the risk of cardiotoxicity in patients with cancer. Other studies have shown lowering blood pressure improves the health of patients. However, these studies have not included people with cancer.

The PROTECT trial is testing a treatment strategy regarding intensive versus standard SBP goals, and is not testing specific medications.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Cardiotoxicity
• Intervention / Treatment: Other: antihypertensive medications; Diagnostic test: Blood pressure measurement; Diagnostic test: Echocardiogram; Other: Symptom-limited cardiopulmonary exercise test; Other: Quality of Life Measures; Diagnostic test: Biomarkers

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anthony Yu, MD; Phone Number: 212-639-7932; Email: yua3@mskcc.org
• Study Contact Backup: Name: Jennifer Liu, MD; Phone Number: 212-639-8220

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Anthony Yu, MD; Phone Number: 212-639-7932
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Anthony Yu, MD; Phone Number: 212-639-7932
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Anthony Yu, MD; Phone Number: 212-639-7932
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
      • Contact: Anthony Yu, MD; Phone Number: 212-639-7932
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Anthony Yu, MD; Phone Number: 212-639-7932
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All protocol activities)
      • Contact: Anthony Yu, MD; Phone Number: 212-639-7932
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Anthony Yu, MD; Phone Number: 212-639-7932

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Female assigned at birth
• Biopsy proven breast cancer (stage I-IV)
• Treatment with therapy anthracycline-based chemo (with or without HER2-targeted therapy), with >/= 2 cycles of anthracycline chemotherapy planned.
• SBP ≥130 mm Hg
• Willing and able to comply with the requirements of the protocol.
• Participant must have and be willing to use their bluetooth enabled wifi or cellular mobile device

• (For participants in the CPET cohort): Able to complete an acceptable baseline CPET, in the absence of high-risk ECG findings or other inappropriate response to exercise as determined by the PI, as defined by any of the following criteria:

  • Achieving a plateau oxygen consumption, concurrent with an increase in power output;
  • A respiratory exchange ratio ≥ 1.10;
  • Attainment of maximal predicted heart rate, as defined by a peak heart rate within 10bpm of the age predicted maximal heart rate (220 - Age[years]);
  • Volitional exhaustion, as measured by a rating of perceived exertion (RPE) ≥ 18 on the BORG scale.

Exclusion Criteria:

• eGFR < 30 ml/min/1.73m2 (based upon Cockcroft-Gault, etc.)
• Individuals with arm circumference too large to allow accurate BP measurement with available BP devices
• Inability to accurately measure blood pressure in at least one arm (e.g., bilateral upper extremity lymphedema)

• Cardiac comorbidity, including any of the following:

  • Acute coronary syndrome within 3 months prior to randomization.
  • Symptomatic heart failure (NYHA class III/IV) within past 6 months
  • History of stroke
  • Cardiac transplantation
• Other medical disorder or condition that in the opinion of the investigator would impair the subject's ability to participate or adhere to study interventions

• (For participants in the CPET cohort): Subjects must not have any of the following absolute contraindications to cardiopulmonary exercise testing:

  • Acute myocardial infarction (within 30 days of any planned study procedures),
  • Unstable angina
  • Uncontrolled arrhythmias causing symptoms or hemodynamic compromise,
  • Symptomatic severe aortic stenosis
  • Recurrent syncope
  • Active endocarditis
  • Acute myocarditis or pericarditis
  • Acute pulmonary embolus or pulmonary infarction (within 3 months of any planned study procedures)
  • Thrombosis of lower extremities (within 3 months of any planned study procedures)
  • Suspected dissecting aneurysm
  • Uncontrolled asthma
  • Pulmonary edema
  • Room air desaturation at rest ≤85%
  • Respiratory failure
  • Acute noncardiopulmonary disorder that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)
  • Mental impairment leading to inability to cooperate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: standard-of-care antihypertensive medications; 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.	Other: antihypertensive medications; One or more of the following medications may be used in both randomization groups to achieve SBP goals: Angiotensin converting enzyme inhibitors (ACEI); Angiotensin receptor blockers (ARBs); Beta-blockers (BB); Thiazide-type diuretics; Calcium channel blockers; Aldosterone antagonists; Alpha1-receptor blockers.; Direct vasodilators; Loop diuretics; Diagnostic test: Blood pressure measurement; Home BP Monitoring (HBPM)-Throughout the study period, patients will perform HBPM at baseline, month 6, and month 12 (end of treatment). At each of these timepoints, HBPM will be performed for 7 days with 2 morning and 2 evening readings for each day (measured 1-min part).; Diagnostic test: Echocardiogram; At baseline, month 6, and month 12; Other: Symptom-limited cardiopulmonary exercise test; Consecutive patients in each treatment group who meet the eligibility criteria for exercise testing will be offered to participate in CPET at the time of consent. Patients who agree will undergo CPET (baseline, 6 months, and 12 months) until the target accrual of 33 patients per group is met.; Other: Quality of Life Measures; FACT-B, Fatigue Symptom Inventory (FSI), Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale, Godin Leisure Time Exercise Questionnaire (GLTEQ),PROMIS Medication Adherence Scale. Given baseline, 3 months and 12 months.; Diagnostic test: Biomarkers; Research blood samples will be collected at baseline, 3 months, and 6 months
Experimental: higher dose antihypertensive medications; 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.	Other: antihypertensive medications; One or more of the following medications may be used in both randomization groups to achieve SBP goals: Angiotensin converting enzyme inhibitors (ACEI); Angiotensin receptor blockers (ARBs); Beta-blockers (BB); Thiazide-type diuretics; Calcium channel blockers; Aldosterone antagonists; Alpha1-receptor blockers.; Direct vasodilators; Loop diuretics; Diagnostic test: Blood pressure measurement; Home BP Monitoring (HBPM)-Throughout the study period, patients will perform HBPM at baseline, month 6, and month 12 (end of treatment). At each of these timepoints, HBPM will be performed for 7 days with 2 morning and 2 evening readings for each day (measured 1-min part).; Diagnostic test: Echocardiogram; At baseline, month 6, and month 12; Other: Symptom-limited cardiopulmonary exercise test; Consecutive patients in each treatment group who meet the eligibility criteria for exercise testing will be offered to participate in CPET at the time of consent. Patients who agree will undergo CPET (baseline, 6 months, and 12 months) until the target accrual of 33 patients per group is met.; Other: Quality of Life Measures; FACT-B, Fatigue Symptom Inventory (FSI), Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale, Godin Leisure Time Exercise Questionnaire (GLTEQ),PROMIS Medication Adherence Scale. Given baseline, 3 months and 12 months.; Diagnostic test: Biomarkers; Research blood samples will be collected at baseline, 3 months, and 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean change in systolic blood pressure (SBP) from baseline to 12 months	based upon in-office measurement	12 months

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Anthony Yu, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): May 30, 2029

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Blood pressure; 23-159
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Neoplasms; Heart Diseases; Chemically-Induced Disorders; Skin Diseases; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Breast Neoplasms; Cardiotoxicity; Diagnostic Techniques and Procedures; Diagnosis; Biological Factors; Public Health; Environment and Public Health; Diagnostic Imaging; Biological Phenomena; Diagnostic Techniques, Cardiovascular; Physical Examination; Heart Function Tests; Cardiac Imaging Techniques; Ultrasonography; Biomarkers; Environmental Pollution; Environmental Monitoring; Environmental Exposure; Echocardiography; Blood Pressure Determination; Environmental Biomarkers
• Other Study ID Numbers: 23-159

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No