Investigators at the UCLA Health Jonsson Comprehensive Cancer Center have opened a clinical trial that will look at whether combining precision radiation with a targeted radioactive therapy drug can help patients with recurrent prostate cancer delay progression, while delaying or avoiding the side effects of long-term hormone therapy.
The Phase 2 trial, called ANDROMEDA, is the first study to directly compare two types of PSMA-targeted radiopharmaceuticals—lutetium-177–PSMA-617 (lutetium Lu 177 vipivotide tetraxetan) and actinium-225–PSMA-617—when used alongside stereotactic body radiotherapy (SBRT), a focused form of radiation that treats all detectable tumors.
PSMA, or prostate-specific membrane antigen, is a protein found on the surface of most prostate cancer cells. This makes it an ideal target for radiopharmaceutical therapy, which delivers radiation directly to cancer cells while sparing surrounding healthy tissue. Lutetium-177 emits beta particles, which travel farther but are less energetic, while actinium-225 emits alpha particles, which are more potent and can deliver a highly localized radiation dose.
The trial is led by Amar Kishan, MD, professor and executive vice chair of radiation oncology and co-director of the cancer molecular imaging, nanotechnology and theranostics program at the UCLA Health Jonsson Comprehensive Cancer Center, and Jeremie Calais, MD, PhD, director of the department of Nuclear Medicine and Theranostics’ clinical research program and associate professor at the David Geffen School of Medicine at UCLA.
“While we have previously shown that adding lutetium-177-based therapy to SBRT can prolong survival without progression in recurrent prostate cancer, we think actinium-225 may be even more effective at targeting microscopic disease,” said Kishan. “By comparing the two treatments head-to-head, we hope to determine which approach provides the most durable cancer control.”
The trial is enrolling men with oligorecurrent prostate cancer, meaning the cancer has come back in 1 to 5 spots, as detected by a PSMA PET scan. Patients in the trial will receive radiation to all detectable tumors and either two cycles of lutetium-177-based therapy or a single cycle of actinium-225-based therapy prior to SBRT. Their progress will be tracked using follow-up imaging and blood tests, as well as patient-reported quality-of-life measures.
Researchers hope the combination can delay, or possibly even prevent, the need for hormone therapy, which often comes with fatigue, hot flashes, bone loss and other long-term side effects.
“By combining whole-body targeted radiopharmaceutical therapy with precise local radiotherapy, we hope to eliminate both visible tumors and microscopic disease,” said Calais. “The ultimate goal is to improve long-term cancer control while preserving quality of life.”
The ANDROMEDA trial builds on earlier research, including the LUNAR trial, which showed encouraging early results combining targeted lutetium-177-based therapy and SBRT. This study represents the next step in exploring how these treatments can work together to treat oligorecurrent prostate cancer more effectively.
Individuals interested in participating can find more information at clinicaltrials.gov or contact Sophia Parmisano at [email protected] or 310-825-9775.
