Implantable Device Helps Predict Drug Therapy Efficacy

 

Dana-Farber investigators recently launched a trial of a miniature device that can be implanted into ovarian tumors to deliver microdoses of different drugs, with the goal of rapidly measuring their effectiveness in killing cancer cells. The researchers hope the method could shorten the time needed to determine if a drug is helping a patient, and potentially be a useful tool in personalizing drug therapies.

The device, smaller than a grain of rice, contains reservoirs that can hold up to 20 microdoses of chemotherapy drugs and combinations. It remains in the tumor for about 24 hours, with nearby cancer cells being exposed to the drugs in their native environment. Then, the device and a sample of surrounding tissue are removed during a surgical procedure that was already scheduled as part of the patient’s treatment.

The investigators propose that examination of the tissue sample will reveal whether the cancer cells are sensitive or resistant to the drugs — potentially in a matter of days. The pilot study is designed only to evaluate the feasibility of the procedure, and findings will not be used to guide treatment.

“Once optimized, the microdevice may be able to predict the efficacy of specific drugs for each patient’s tumor and inform therapeutic decision-making,” according to a description of the clinical trial.

Measuring drug responses

The study, led by Elizabeth Stover, MD, PhD, a medical oncologist in Gynecologic Oncology at Dana-Farber, is in a feasibility phase and has begun enrolling patients diagnosed with advanced ovarian, fallopian tube, or primary peritoneal cancers. Several microdevices will be implanted into the tumor in a minimally invasive procedure. The patients will have previously been scheduled to undergo surgery to remove as much of the tumor as possible; the microdevices will be removed as part of this procedure.

Elizabeth Stover, MD, PhD.Elizabeth Stover, MD, PhD.

Stover notes that because the drugs diffuse a short distance into the adjacent tumor tissue, the microdevice allows for “measuring drug responses within the tumor itself, as well as immune cells, supporting cells, and others — and it is very efficient for testing multiple drugs simultaneously.”

In the feasibility study, Stover says, the microdevices will be delivering standard chemotherapy drugs such as cisplatin, carboplatin, doxorubicin, and PARP inhibitors. In the future, investigational drugs could be tested with this method.

The microdevice was developed by Oliver Jonas, PhD, of Brigham and Women’s Hospital and the Dana-Farber/Harvard Cancer Center. In addition to the ovarian cancer project with Stover, Jonas is collaborating on trials with Cecilia Larocca, MD, also of Dana-Farber, in cutaneous T-cell lymphoma (CTCL); Adam Kibel, MD, in prostate cancer, and Pier Paolo Peruzzi, MD, PhD, in glioblastoma.

“We’ve had about 30 patients that have had devices implanted prior to surgery and then retrieved with the surgical specimen,” Jonas says. “The long-term goal is to use the data to predict therapy, though the current studies are not powered to assess that definitively.”

Jonas is also working to develop implantable devices that could deliver drugs to a tumor without the need for surgery to remove it. This microdevice would deliver, along with the drugs, a fluorescent compound that could measure cancer cell death, and could be imaged by a scan while remaining in the tumor. He calls this concept a “lab in a tumor.”

Stover’s research is supported by the Kathryn Fox Samway Foundation, the Wong Family Award, and the Massachusetts Life Sciences Center.