Cancer and Blood Pressure Management, CARISMA Study
Cancer and Blood Pressure Management, CARISMA Study
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.
PRIMARY OBJECTIVE:

 I. 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.
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)