Cancer and Blood Pressure Management, CARISMA Study

Sponsor

ECOG-ACRIN Cancer Research Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT04467021

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

43.2

Anticipated Duration (Months)

2.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies how well intensive blood pressure management works in decreasing systolic blood pressure in patients with kidney or thyroid cancer that has spread to other places in the body (metastatic) who are starting anti-angiogenic tyrosine kinase inhibitor cancer therapy. This study is being done to find out if a systolic blood pressure to a target of less than 120 mmHg (intensive systolic blood pressure management) can be achieved, well tolerated, and beneficial as compared to the usual approach to a target of less than 140 mmHg while taking an anti-angiogenic tyrosine kinase inhibitor. This study may help doctors understand the best way to control blood pressure in kidney or thyroid cancer patients taking anti-angiogenic tyrosine kinase inhibitor.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disorder Chronic Kidney Disease Metastatic Renal Cell Carcinoma Metastatic Thyroid Gland Medullary Carcinoma Stage IV Renal Cell Cancer AJCC v8 Stage IV Thyroid Gland Medullary Carcinoma AJCC v8 Stage IVA Thyroid Gland Medullary Carcinoma AJCC v8 Stage IVB Thyroid Gland Medullary Carcinoma AJCC v8 Stage IVC Thyroid Gland Medullary Carcinoma AJCC v8	Other: Best Practice Other: Blood Pressure Measurement Other: Clinical Management Other: Quality-of-Life Assessment Other: Questionnaire Administration	N/A

Detailed Description

PRIMARY OBJECTIVE:

To determine the feasibility of an intensive (systolic blood pressure [SBP] < 120 mmHg) "Intervention" versus standard care (SBP < 140 mmHg) "Non-Intervention" approach to blood pressure (BP) control in metastatic renal cell and thyroid cancer patients initiating anti-angiogenic tyrosine kinase inhibitors.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive intensive systolic blood pressure management for 6 months. Patients receive increased blood pressure medication every 2 weeks while systolic blood pressure is 120 mmHg or higher. Patients also monitor blood pressure at home 1 day a week (4 times in 1 day) every 2 weeks and upload the recorded blood pressure readings to the provider and to a central blood pressure monitoring team. Patients with changes in blood pressure medications monitor blood pressure readings on 3 days in 1 week (4 times in 1 day).

ARM B: Patients receive standard blood pressure management for 6 months. Patients receive blood pressure medications per doctor's instruction. Patients also monitor blood pressure at home 1 day (4 times in 1 day) every 2 weeks and upload the recorded blood pressures to a central monitoring team.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cancer Therapy Risk-Reduction With Intensive Systolic BP Management (CARISMA) - a Phase II Study

Actual Study Start Date :

Sep 1, 2020

Anticipated Primary Completion Date :

Oct 9, 2023

Anticipated Study Completion Date :

Apr 9, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (intensive systolic blood pressure management) Patients receive intensive systolic blood pressure management for 6 months. Patients receive increased blood pressure medication every 2 weeks while systolic blood pressure is 120 mmHg or higher. Patients also monitor blood pressure at home 1 day a week (4 times in 1 day) every 2 weeks, and upload the recorded blood pressure readings to the provider and to a central blood pressure monitoring team. Patients with changes in blood pressure medications monitor blood pressure readings on 3 days in 1 week (4 times in 1 day).	Other: Blood Pressure Measurement Undergo blood pressure measurement Other: Clinical Management Undergo intensive systolic BP management Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies
Active Comparator: Arm B (usual blood pressure management) Patients receive standard blood pressure management for 6 months. Patients receive blood pressure medications per doctor's instruction. Patients also monitor blood pressure at home 1 day (4 times in 1 day) every 2 weeks, and upload the recorded blood pressures to a central monitoring team.	Other: Best Practice Receive usual blood pressure management Other Names: standard of care standard therapy Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies

Arm

Intervention/Treatment

Experimental: Arm A (intensive systolic blood pressure management)

Patients receive intensive systolic blood pressure management for 6 months. Patients receive increased blood pressure medication every 2 weeks while systolic blood pressure is 120 mmHg or higher. Patients also monitor blood pressure at home 1 day a week (4 times in 1 day) every 2 weeks, and upload the recorded blood pressure readings to the provider and to a central blood pressure monitoring team. Patients with changes in blood pressure medications monitor blood pressure readings on 3 days in 1 week (4 times in 1 day).

Other: Blood Pressure Measurement

Undergo blood pressure measurement

Other: Clinical Management

Undergo intensive systolic BP management

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Questionnaire Administration

Ancillary studies

Active Comparator: Arm B (usual blood pressure management)

Patients receive standard blood pressure management for 6 months. Patients receive blood pressure medications per doctor's instruction. Patients also monitor blood pressure at home 1 day (4 times in 1 day) every 2 weeks, and upload the recorded blood pressures to a central monitoring team.

Other: Best Practice

Receive usual blood pressure management

Other Names:

standard of care

standard therapy

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Questionnaire Administration

Ancillary studies

Outcome Measures

Primary Outcome Measures

Differences in systolic blood pressure (SBP) based on automated office BP measurements [Up to 6 months]
Differences in SBP over the 6- month study period between intensive BP control (intervention) versus standard care (non-intervention group) will be compared using the "difference-indifference" method. All mixed effects models will be estimated using generalized estimating equations (GEE).

Secondary Outcome Measures

Difference in SBP based on all automated home and office BP measurements [Up to 6 months]
Based on all automated home and office BP measurements.
Study retention rates [Up to 6 months]
Will compare the study retention rates between the intensive SBP versus standard care group, by constructing appropriate mixed-effect generalized linear models (e.g. a mixed effect log-linear model for fatigue and a logistic model for study retention) and using GEE for model estimation
Frequency of automated home SBP measurements > 180 mmHg or < 90 mmHg or diastolic (D)BP > 110 mmHg [Up to 6 months]
The frequency of orthostatic hypotension as defined by > 20 mmHg decreases in office SBP with standing; or symptomatic hypotension, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) criteria, in participants in the intervention and non-intervention group arms.
Differences in symptoms and health-related quality of life [Up to 6 months]
Will compare the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue between the intensive SBP versus standardlcCare group, by constructing appropriate mixed-effect generalized linear models (e.g. a mixed effect log-linear model for fatigue and a logistic model for study retention) and using GEE for model estimation.
Differences in patient-reported medication compliance [Up to 6 months]
Will compare the medication compliance between the intensive SBP versus standard care group, by constructing appropriate mixed-effect generalized linear models (e.g. a mixed effect log-linear model for fatigue and a logistic model for study retention) and using GEE for model estimation.
Patient-rated adverse events associated with hypertension, hypotension and anti-hypertensive medications [Up to 6 months]
Participant satisfaction with BP care [Up to 6 months]
The participant satisfaction with BP care (including the C-BAC and the related technologies) and BP medications will be evaluated through questionnaires evaluated on a Likert scale and via open ended discussions with focus groups.
Provider satisfaction with BP care [Up to 6 months]
The provider satisfaction with BP care (including the C-BAC and the related technologies) and BP medications will be evaluated through questionnaires evaluated on a Likert scale and via open ended discussions with focus groups.

Other Outcome Measures

Incidence of significant cardiovascular (CV) events [Up to 6 months]
Will determine the rates of adverse cardiovascular events in each group. These include the incidence of significant CV events including stroke, acute coronary syndrome/myocardial infarction or hospitalization for heart failure; the suspension of anti-angiogenic tyrosine kinase inhibitors therapy due to toxicity; or all-cause death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

English speaking
Patient must have histologically or cytologically-proven advanced metastatic renal cell cancer (mRCC) or medullary thyroid cancer initially treated with anti-angiogenic tyrosine kinase inhibitors (AA-TKIs) including: sunitinib, sorafenib, pazopanib, cabozantinib, lenvatinib, vandetanib, or axitinib)
NOTE: If patient has a severe sulfa allergy (e.g. Stevens Johnson reaction), then alternative non-sulfa medications can be considered in consultation with the C-BAC. Patient with a noted severe allergic reactions to medications listed in the algorithms is not necessarily excluded from this trial, as alternative medications could be considered in consultation with the C-BAC. Moreover, the patient treated with pre-existing medications that may interact with proposed BP medications is not necessarily excluded, as alternative medications exist. The clinical significance of any potential drug interactions can also be addressed with the C-BAC.
Prior exposure to another AA-TKI is permissible. Concurrent or prior treatment with immunotherapy is also permissible
Patient must have either clinical cardiovascular (CV) disease or evidence of increased

CV risk as defined by one or more of the following:

Clinical CV disease (history of myocardial infarction [MI] acute coronary syndrome, coronary revascularization, carotid endarterectomy or stenting greater than 3 months prior to registration, peripheral artery disease, cerebrovascular accident greater than 3 months prior to registration, abdominal aortic aneurysm or heart failure [HF])
An American College of Cardiology/American Heart Association (ACC/AHA) CV risk score of at least 10%
Chronic kidney disease (defined as an estimated glomerular filtration rate [eGFR] between 30 and 60 ml/min per 1.73 m^{2). Dialysis patients and patients with an
eGFR < 30 ml/min/1.73m}2 will be excluded. eGFR will be calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation
Patient must have systolic blood pressure (SBP) >= 130 mmHg on two or more occasions according to any in-clinic visit in the 12 weeks prior to or during their initial 4 weeks of treatment with an AA-TKI. Patient who have a prior diagnosis of hypertension or on pre-existing anti-hypertensive medications are eligible for enrollment. However, patient must not be on more than 3 baseline blood pressure medications at time of entry
NOTE: If a patient has a single elevated SBP >= 130mmHg but not on repeat assessment, an additional SBP assessment should be performed to confirm ineligibility
Patient must agree to comply with performing home blood pressure monitoring using an Omron7250 oscillometric monitor at home, or equivalent models
Women of childbearing potential and sexually active males must be strongly advised to use accepted and effective methods of contraception or to abstain from sexual intercourse for the duration of their participation in the study
Patient must have internet access through a computer, tablet, or smart phone to use EASEE-PRO and home BP monitoring. A valid phone number to receive text messages and email address are also necessary
Leukocytes >= 3,000/mcL (obtained within 14 days prior to registration)
Absolute neutrophil count >= 1,500/mcL (obtained within 14 days prior to registration)
Platelets >= 100,000/mcL (obtained within 14 days prior to registration)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration)
Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patient with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patient with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
Patient with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
Patient with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

Patient must not have end-stage renal failure on dialysis, history of repeated hyperkalemia with a potassium > 5.5 mEq/l, or have a kidney transplant, or an eGFR < 30 ml/min/1.73 m^2
Patient must not have coronary artery bypass grafting, MI acute coronary syndrome severe/unstable angina, stroke, transient ischemic attack, clinically significant bleeding requiring hospitalization or pulmonary embolism within 3 months prior to registration
Patient must not have brain surgery or radiotherapy within 2 weeks prior to registration
Patient must not have uncontrolled blood pressure defined by SBP > 160 mmHg on three or more antihypertensives prior to TKI initiation
Patient with an arm circumference too large (> 50 cm) or small (< 17 cm) to allow accurate BP measurement with available devices will not be eligible
Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with some anti-hypertensives, including angiotensin receptor blockers. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	United States	63141
2	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
3	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
4	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
5	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
6	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
7	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
8	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
9	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
10	Aurora Saint Luke's South Shore	Cudahy	Wisconsin	United States	53110
11	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
12	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
13	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
14	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
15	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
16	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
17	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
18	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
19	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
20	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
21	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
22	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
23	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
24	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
25	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227