Alberta Cancer Foundation

How a clinical trial gets to the heart of cancer

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BREAKTHROUGH TRIAL: Dr. Edith Pituskin and Dr. Ian Paterson worked on a clinical trial that made great strides in cardio-oncology.

In October 2011, Sherwood Park resident Deb Cameron went in for a routine mammogram. She had none of the symptoms typically experienced by breast cancer patients, such as a burning feeling, rash or change in her nipples. She also had no family history of the disease. Still, at the age of 56, Cameron was diagnosed with an aggressive form of breast cancer.

“Cancer treatments have improved greatly to the point where people with early breast cancer are now at a higher risk of cardiovascular disease than they are of recurrent breast cancer,” says Dr. Edith Pituskin.

Before her diagnosis, Cameron was very active and feeling good, which added to her shock. Turning to her radiologist, she said, “If you had told me that I had colon cancer, I probably would have been less surprised.” Cameron was 29 when her mother was diagnosed with a form of colon cancer that doctors said could be genetic. Her mother passed away three years and three surgeries post-diagnosis.

In late November 2011, a nurse at Edmonton’s Cross Cancer Institute, Diane Bodnar, met Cameron at a regular post-diagnosis appointment. Bodnar discussed the potential of Cameron joining a clinical trial. Cameron agreed, and a month later she met Dr. Edith Pituskin, an assistant professor of nursing and oncology at the University of Alberta’s nursing and medicine departments, for her first chemotherapy treatment at the Cross. Pituskin is a co-investigator on the clinical trial known as MANTICORE.

“My mom joined a chemo clinical trial when she was diagnosed,” Cameron says. “Knowing that my mom participated in a trial definitely made me feel that if my mom can do it, I can do it.” Her husband and two daughters were also supportive of her joining a clinical trial. “We all felt that, with every advancement that’s been made in cancer treatment, somebody else has probably gone through a type of trial to advance the levels of treatment.”

One of her daughters was pregnant when Cameron was diagnosed, and her third grandchild was born soon after letting the whole family know she had cancer. She says her new baby grandson became her comfort, something else to focus on when he visited her during chemo treatments.

Pituskin was involved in developing the MANTICORE trial, but it actually began years earlier. In 2006, Dr. John Mackey, a professor in medical oncology at the -University of Alberta and director of the Clinical Trial Unit at the Cross Cancer Institute, and Dr. Mark Haykowsky, a physical therapy professor in the Faculty of Rehabilitation Medicine at the University of Alberta, were studying heart weakening in cancer patients taking a drug called Herceptin. They wondered if exercise could play a role in prevention, and invited Dr. Ian Paterson, a cardiologist at the University of Alberta Hospital, to join them in a small study to test the connection, while Pituskin recruited the study’s patients.

“We found that exercise did not prevent the heart changes as we had hoped it would,” Paterson says. As a cardiologist, Paterson’s go-to remedy typically involves giving patients medication. “Giving pills is easier than convincing someone to do exercise,” he says. So he started a new study that used heart medications to prevent Herceptin–related heart weakening. His randomized, placebo-controlled clinical trial was called MANTICORE, an acronym for Multidisciplinary Approach to Novel Therapies In Cardiology Oncology Research. “It also happens to be a creature from the game Dungeons & Dragons,” Paterson says, “and thus, a tribute to my nerdy adolescent years.”

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HEART MONITOR: Dr. Ian Paterson checks up on Deb Cameron, who participated in the Herceptin clinical trial. Photo courtesy University of Alberta

Funding support for the trial came from the Canadian Institutes for Health Research as well as other groups including the Alberta Cancer Foundation.

“The [typical] approach in cardiology is that we give heart pills after the problem has developed,” Paterson says. “But in this case, we wanted to see if giving pills as a prevention strategy from day one of their chemo, which is also day one of Herceptin in their case, would help prevent heart weakening and ultimately heart failure.”

The MANTICORE study began in December 2010, with Paterson as lead investigator and Pituskin as co-investigator and study manager. Pituskin recruited patients, like Cameron at the Cross, and met with them during their treatments. The study included 99 breast cancer patients from Edmonton and Winnipeg who were HER2-positive, in the early stages of the breast cancer and had no prior heart problems. Cameron fit all of those requirements.

HER2-positive breast cancer is a more aggressive form of the disease that affects roughly one in five breast cancer patients. These patients receive standard cancer treatments (like chemotherapy and surgery, if needed) in addition to Herceptin, an effective drug to treat breast cancer that can also weaken a patient’s heart.

About 90 per cent of the patients in the study were receiving treatment in Edmonton, with the rest in Winnipeg. At the time, many sites were approached to partner in the study, but some didn’t have timely access to a cardiac MRI. That equipment was necessary for the study to enable investigators to effectively monitor patients’ hearts throughout their cancer treatment. Investigators routinely checked participants for any heart muscle weakening or function, which can happen not only during cancer treatment but also years later.

Patients were asked to participate in the trial for two out of the five years it ran, between December 2010 and December 2015. For the first year, patients took Herceptin, received regular chemo treatments and also took one of three randomly selected drugs: a placebo, a beta blocker or an ACE inhibitor. Beta blockers and ACE inhibitors are used to treat heart failure in addition to several other conditions. During the second year, patients returned for heart checkups and had blood samples taken to monitor their health.

The drugs in the study, meant to take a preventive approach to heart failure, were made to look identical, called “blinding.”

“A proper study is randomized so people have an equal chance of getting all the treatment options and it’s blinded,” Pituskin says. “The medications were made by an outside group, and there was no way to know what the study capsules contained – whether it was a placebo or one or the other medications.”

The drug types were split evenly among the group, with 33 patients each getting one type of the study’s drugs for the first year they were involved in he trial – and it’s game changing findings – garnered interest from oncologists around the world.

“We think this is a whole new field,” Pituskin says. “Cancer treatments have improved greatly to the point where people with early breast cancer are now at a higher risk of cardiovascular disease than they are of recurrent breast cancer.”

Over the two years she was involved the trial, Cameron says she had four MRIs of her heart. “Every time we had our MRI, Dr. Paterson would explain to us what they saw, and for me, he said there were only minimal changes and those could have been just because of decreased activity during my chemo,” she says.

The randomized selection of drugs was blind to the patients as well, even after its five-year span concluded in December 2015. “My heart function still seems to be very healthy,” Cameron says, guessing she received something other than a placebo, although she doesn’t know for sure. Patients will be notified in the upcoming year which drug they actually received.

“I had already agreed to take a drug that could be harmful to my health (Herceptin) and by participating in the clinical trial, I could be getting something that would offset that harmful effect,” Cameron says, adding that the clinical trial was a “no brainer” to her, considering it offered her the chance of helping herself and future generations.

“Being part of a clinical trial brought me in contact with other cancer patients, which led to a lot of open discussion because it’s hard to talk to people that haven’t been there and just don’t get it,” Cameron says. “Meeting people in the clinical trial gives you more areas of support, but I also felt there was another set of professional eyes watching me from a different perspective.”

Paterson says during the trial he learned a lot about cancer, cancer treatment and patients, since his work prior had not been in oncology. “I think a study like this helps raise awareness for cancer patients, oncologists and cardiologists and that there may be effective ways to prevent heart weakening,” he says.

Pituskin agrees: “Cardio-oncology is going to be an entirely new and increasingly important area of care,” she says. “And this study is one of the first to show that this is important.”

Cameron had a mastectomy and reconstructive surgery in August 2013. “There are no signs of active cancer in my body,” she says, adding that she is basically in remission but with her type of cancer, she’ll never be considered “cancer-free.”

“In the last three years, between my treatment and reconstruction, I don’t think I’m back to the same physical strength that I was then, but I’m also getting older, so it’s hard to know,” Cameron says. She’s back to running, walking and doing yoga to stay active.

“The future for me is to continue to be active, health-conscious and stay involved with my family and with other survivors,” she says. “But mainly, just trying to live my life beyond cancer.”


For more information on clinical trials, and how to get involved, visit www.albertacancerclinicaltrials.ca