# Planning Grant for CARISMA - Cancer therapy Risk-reduction with Intensive Systolic BP Management

> **NIH NIH R34** · UNIVERSITY OF PENNSYLVANIA · 2020 · $371,449

## Abstract

PROJECT SUMMARY
Cancer has become increasingly treatable as a chronic disease, largely as a result of the rapid expansion of
highly effective, targeted anti-cancer therapies, used singly or in combination. Unfortunately, treatment-related
cardiovascular (CV) toxicity has emerged as an important contributor to morbidity and mortality in cancer
patients. For example, anti-angiogenic tyrosine kinase inhibitors (AA-TKIs) are first-line therapies in metastatic
renal cell and thyroid cancers, which have a combined incidence of over 600,000 new cases each year. However,
AA-TKIs are also associated with significant CV toxicity, with hypertension in at least half of patients and left
ventricular dysfunction in 10 to 15%. Such toxicities can result in dose reductions, treatment interruptions,
cessation of necessary therapy, and ultimately worse overall survival. This has resulted in a need to develop
evidence-based strategies to mitigate CV toxicity to improve not only CV but also oncologic outcomes.
In non-cancer populations, SPRINT demonstrated that intensive systolic blood pressure (SBP) lowering to a
target <120mmHg substantially reduces the rate of CV events and all-cause mortality. Though cancer patients
who develop CV risk factors such as hypertension or CV disease have worse morbidity and mortality than
noncancer comparators, concerns about the tolerability of intensive SBP control limit application of guidelines
for aggressive SBP targets in clinical practice. Moreover, patients with cancer were largely excluded from
SPRINT. As a result, the optimal SBP target remains unknown among patients receiving targeted cancer
therapies. Compelling evidence establishing the impact of intensive SBP control is an important unmet need.
Our ultimate objective is to perform a Phase III randomized clinical trial (RCT) to test the hypothesis that intensive
SBP lowering to a target of <120 mmHg, as compared to Usual Care, is well-tolerated and beneficial in cancer
patients receiving AA-TKIs. The RCT will be performed within the NCI-funded ECOG-ACRIN Cancer Research
Group in partnership with the NHLBI-funded Heart Failure Network. This planning grant is designed to inform
the design and execution of our Phase III RCT by addressing the following Specific Aims: In Aim 1, we will
perform a retrospective analysis to define the distributions of SBP, CV risk scores, incidence of CV events, and
all-cause mortality rates in patients treated with AA-TKIs for metastatic renal cell and thyroid cancers. In Aim 2,
we will perform a 50-patient prospective pilot study using a site-based cluster randomization design amongst 4
ECOG-ACRIN sites comparing ‘Intensive SBP Control’ with ‘Usual Care.’ This will be facilitated by a centralized
BP Advisory Core, and will inform the SBP trajectories, safety and tolerability of Intensive SBP control, and
participant and site burden. These studies will provide the necessary and sufficient data to launch a Phase III
RCT trial that will guide the...

## Key facts

- **NIH application ID:** 9987753
- **Project number:** 5R34HL146927-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Bonnie Ky
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,449
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987753

## Citation

> US National Institutes of Health, RePORTER application 9987753, Planning Grant for CARISMA - Cancer therapy Risk-reduction with Intensive Systolic BP Management (5R34HL146927-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987753. Licensed CC0.

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