Penn Medicine launches first human clinical trial to test precision form of FLASH proton therapy

A new form of proton therapy—designed to deliver cancer-killing radiation therapy in less than a second, through fewer total sessions, with potentially less risk of damaging side effects—is now being tested in a Phase I clinical trial at the Abramson Cancer Center of the University of Pennsylvania. Known as FLASH proton therapy, the feasibility study represents the first time that the “conformal,” or precise 3D targeting, version of the technique has been tested in human patients in the United States.

The study will enroll 10 patients whose head and neck cancer has returned after previous radiation treatment and who are not candidates for surgery to remove the cancer. This study population was selected because of the potential quality of life benefits that FLASH proton therapy could offer. Patients with recurrent head and neck cancer typically face a difficult prognosis, complicated by the side effects of radiation therapy to areas that control important body functions, like the ability to eat, drink, and swallow.

“Patients with recurrent, unresectable head and neck cancer have limited treatment options, and the options they do have, like repeat radiation, are incredibly grueling, not only in terms of potentially life-altering side effects, but also in terms of time spent in medical facilities,” said principal investigator Alexander Lin, MD, the Morton M. Kligerman Professor of Radiation Oncology in Penn’s Perelman School of Medicine. “Radiation therapy impacts these patients’ lives in ways that are hard to appreciate. We want to be able to offer a treatment with minimal toxicity that's easy and convenient so that patients can spend more time with family and friends.”

A typical radiation therapy regimen for these patients would involve daily treatment over five to six weeks. The FLASH protocol will only require five treatments over about 10 days.

The clinical trial will be conducted at the Roberts Proton Therapy Center located inside Penn Medicine’s Perelman Center for Advanced Medicine in Philadelphia. Patients interested in enrolling should contact study coordinator Ching Lai at 267-250-9244 or Ching.Lai@pennmedicine.upenn.edu.

Radiation therapy is one of the pillars of cancer treatment, along with chemotherapy, surgery, and immunotherapy. Proton therapy is an advanced form of radiation therapy that uses high-energy protons (positively charged atoms) to damage the DNA in cancer cells and destroy them. Penn Medicine is currently building its fourth proton therapy center at Penn Presbyterian Medical Center, expected to open for patients in late 2027.

Penn Medicine is a global leader in FLASH research and recently completed a FLASH proton therapy clinical trial for pet dogs with cancer in collaboration with the School of Veterinary Medicine. The canine study used the same technology for head and neck cancer that will be applied in this trial for human patients.

“The conventional wisdom of radiation therapy focused on ‘fractionation,’ or spreading out the total dose of radiation therapy into smaller doses given over long periods of time to kill tumor cells and spare healthy tissue,” said Constantinos Koumenis, PhD, the Richard H. Chamberlain Professor of Radiation Oncology at Penn Medicine.

All forms of radiation therapy, including proton therapy and intensity-modulation radiation therapy (IMRT), are currently fractionated. For a patient with head and neck cancer, this typically means 25-35 fractions of radiation, one per day, five days a week, for five to six weeks total. “FLASH turns this idea on its head,” Koumenis said.

Instead of using smaller doses to mitigate the effects of radiation, FLASH uses a larger dose and shrinks the amount of time the patient is treated with radiation. The total effective dose of radiation remains the same, but it’s divided into a smaller number of fractions—each one given in a large, lightning-fast dose. Patients participating in the clinical trial will receive FLASH proton therapy five times total, with each exposure lasting less than a second. Patients will complete all five sessions in less than two weeks.

Most cancer radiation therapy involves conformal therapy, which means that the radiation is delivered to the exact boundaries set by the treatment team so that they can avoid damage—as much as possible— to healthy tissues around the tumor. This is done by taking imaging exams (such as CT scans or MRI) to create a 3D map of the tumor to direct the radiation beam with pinpoint accuracy.

The type of FLASH proton therapy used in this clinical trial is known as ConformalFLASH® proton therapy and was approved by the FDA through an Investigational Device Exemption (IDE) to Ion Beam Applications S.A. (IBA), the company that manufactures the proton therapy platform used in this clinical trial. IBA is also the sponsor of the study.

Previous clinical trials outside of Penn have tested what is known as a “shoot-through” form of FLASH proton therapy for patients whose cancer spread to their bones. In those studies, the proton beam passed directly through the body without conformal 3D mapping.

“By pairing the power of proton therapy with the precision control of conformal techniques, we’re able to evaluate the full potential of FLASH,” said James Metz, MD, chair of Radiation Oncology at the Perelman School of Medicine. “Launching the clinical trial is an important milestone toward understanding the benefits and limitations of this investigational technology.”

Better alignment with patient goals of care

The Penn clinical trial is designed to test the safety and feasibility of the ConformalFLASH® proton therapy approach, with an anticipation that it will give patients better quality of life, with less time spent in the hospital and traveling for treatment. If successful, it’s anticipated to be expanded to other cancer types and to larger Phase II and Phase III clinical trials focused on treatment outcomes.

“Regardless of the technological advances, what matters at the end of the day is how well the treatment is received by the patient—if the balance of the side effects versus outcomes are worth it to them,” Lin said. “We’re hopeful that FLASH proton therapy could provide better alignment of the treatment with a patient or a family's specific goals in the face of a very difficult diagnosis.”