A University of Colorado Anschutz Cancer Center member, Marie Wood, MD, is recruiting women with a certain type of advanced breast cancer for a worldwide clinical trial investigating a pair of new therapies.
The cancer center is the only location in the Rocky Mountains actively recruiting for the trial, known as EvoPAR-Breast01. Researchers want to find out which combination of the new treatments does the best job in controlling cancer the longest and with the fewest side effects.
The phase 3 trial – backed by global pharmaceutical giant AstraZeneca – is being conducted across North and South America and in Europe, Asia, and Australia. At CU Anschutz, Wood is the site principal investigator for the study.
Wood is medical director of the cancer center’s Hereditary Cancer Program and is a professor of medicine in the CU Anschutz Division of Medical Oncology. She recently was granted a five-year Research Specialist Award (R50) by the National Cancer Institute to expand the scope of cancer clinical trials.
Criteria for the trial
Patients may be eligible for the EvoPAR trial if they have:
- HR-positive, HER2-negative breast cancer – a type in which cancer cells have hormone receptors (HR) but do not have high levels of a protein called HER2 that can make breast cancer more aggressive. Roughly 70% of breast cancer cases are HR+/HER2-.
- The cancer or the participant must have a mutation of the tumor-suppressor genes BRCA1, BRCA2, or PALB2.
- The cancer is metastatic, meaning that it has spread to other parts of the body, and it has not been treated since the spread was detected (other than a short course of hormonal therapy).
These patients “tend to have overall poor outcomes,” Wood says, “and this study is looking for ways to improve outcomes.”
Currently, the standard of care for metastatic HR+/HER2- breast cancer is to use endocrine therapy with one of several targeted drugs called CDK4/6 inhibitors. While CDK4/6 inhibitors are generally effective against these cancers, Wood says there is data showing they can be less effective when mutations in BRCA or PALB2 are involved. “So this study is looking at a new partner for endocrine therapy” that might work better, she says.
The treatments being tested in the EvoPAR trial include an AstraZeneca-developed investigational treatment called saruparib, a new generation of targeted drug known as a PARP1 inhibitor. It’s designed to block enzymes that helps repair DNA damage in cancer cells, thereby forcing the cells to die.
Another new treatment being investigated is camizestrant, an endocrine therapy called a selective estrogen receptor degrader (SERD) that breaks down estrogen receptors on the surface of cancer cells, causing cell death.
Wood notes that both saruparib and camizestrant are oral medications (as are CDK4/6 inhibitors), which means trial participants recruited by the cancer center don’t have to come repeatedly to CU Anschutz to take those drugs, “and we will be partnering with their community provider on this.”
Three arms
EvoPAR trial participants are being randomly assigned to one of three treatment groups, or arms:
- Arm 1 is given a combination of saruparib with camizestrant.
- Arm 2 gets treatments already approved by the U.S. Food and Drug Administration: a standard-of-care combination of a CDK4/6 inhibitor plus standard endocrine therapy.
- Arm 3 gets the CDK4/6 inhibitor along with camizestrant.
“We will be answering if the investigational arm (Arm 1) is superior to standard of care treatment. Superior is defined by cancer taking longer to progress,” Wood says. Participants stay on treatment until the cancer worsens, side effects become too difficult, or they choose to leave the study.
Spreading the word
Wood says it’s not easy to find patients who fit all the criteria of the EvoPAR trial, which is one reason there are many sites for the study.
She has been helping to spread the word about the trial, including talking to members of FORCE (Facing Our Risk of Cancer Empowered), a national group focused on hereditary cancers and oncologists across the state.
The study sponsor AstraZeneca is covering the cost of genetic testing of potential trial participants. The goal is to enroll about 500 patients worldwide and to follow them for several years.
The fact that the CU Anschutz Cancer Center is a site for a global study of this scale is a sign of “our ability to attract industry partners to do novel therapeutic strategies,” Wood says.
