- Results from a Phase I clinical trial using focused ultrasound and microbubbles to improve radiation therapy in patients with breast cancer were recently published.
- The combination treatment led to a complete response in seven tumors, with minimal side effects.
A collaborative research team led by Gregory Czarnota, MD, PhD, at Sunnybrook Research Institute and the University of Toronto recently published initial results from their Phase I clinical trial (NCT04431674) using focused ultrasound plus Definity microbubbles to improve the potency of radiation therapy in patients with breast cancer. The focused ultrasound was delivered with Profound Medical Sonalleve device and guided by a Philips Achieva 3T MRI system. Definity microbubbles are FDA-approved and made by Lantheus Medical Imaging.
The first-in-human study enrolled eight women who were 44 to 76 years old. They presented with nine tumors in the breast or chest wall, all of which were diagnosed as invasive ductal carcinoma. All but one participant had metastatic disease. Five of the tumors were hormone receptor–positive (various combinations*) and three were triple negative (TNBC).
Before the first and fifth fractions of radiation, within one hour before administering the radiation therapy, physicians intravenously delivered microbubbles and then applied focused ultrasound to the tumors. The parameters used for focused ultrasound were based on preclinical data (i.e., frequency of 800 kHz, peak negative pressure of 570 kPa). The median volume of focused ultrasound that was applied to the tumors was 24 cc (range 5 to 76 cc) over a median treatment time of 77 minutes for the first treatment (range 49–112 minutes) and 71 minutes for the second treatment (range 27–122 minutes). All participants completed the focused ultrasound part of the study. All tumors were treated with either 5 or 10 total fractions of radiation at standard prescribed doses.
Importantly, in seven of the evaluable eight participants with at least 3 months of follow up, the combination treatment led to a complete response in eight tumors with no evidence of active or recurrent disease at the treatment site, with minimal side effects. There were no systemic complications or allergic reactions to the focused ultrasound or microbubbles. Some acute toxicity within three months of completing radiation was observed, including grade 1 and grade 2 radiation dermatitis.
The research team concluded that combining focused ultrasound, microbubbles, and radiation therapy was safe and a promising treatment for breast cancer. A commonly observed response to the treatment was the formation of fibrosis in the area previously occupied by the tumor. This clinical trial was ongoing, and it enrolled a total of 20 participants. The Focused Ultrasound Foundation funded the extension of the clinical trial.
“The 20-patient study has now been completed. Results are being analyzed, and look very promising,” said Dr. Czarnota. “We have also applied for approvals for a larger, 200-patient study and are negotiating that with Health Canada.”
“This is an encouraging preliminary clinical trial to prove the safety, feasibility, and efficacy of focused ultrasound and microbubbles in combination with radiation therapy,” says Lauren Powlovich, MD, MBA, the Foundation’s associate chief medical officer. “The eventual goal is to reduce the dose of radiation therapy and its subsequent local and systemic side effects.”
*Tumor molecular status (N=9): TNBC = 3, ER+ PR+ HER2- = 4, and ER+ PR- HER2+ = 2