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Trial to look at vismodegib as treatment for orbital basal cell carcinoma
The hedgehog pathway inhibitor has been shown to shrink tumors.
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A proposed clinical trial of vismodegib, a novel once-daily oral therapy, to treat orbital and periorbital basal cell carcinoma should begin recruiting in the spring, according to a physician.
“This is a very good example of bench-to-bedside drug development,” principal investigator Alon Kahana, MD, PhD, told Ocular Surgery News. Erivedge (vismodegib, Genentech) is an inhibitor of hedgehog signaling.
“Hedgehog is a very important pathway in cell biology and proliferation and, as a result, also in some cancers,” he said. “The drug is able to disrupt the abnormal signaling that occurs through this pathway in the cancer.”
The proposed clinical trial would involve approximately 50 patients and be supported by a grant from Genentech along with funds from the University of Michigan Comprehensive Cancer Center and other sources. The main endpoint is visual function after treating the cancer with vismodegib. Additional endpoints will compare vismodegib treatment with other modalities, such as wide excision of the tumor or a combination of vismodegib and surgery.
Kahana, whose research letter on vismodegib was published in JAMA Ophthalmology, said the drug was developed to treat particularly aggressive forms of basal cell carcinoma.
To date, Kahana and his colleagues at the University of Michigan have treated nearly 20 patients with advanced or recurrent orbital/periorbital basal cell carcinoma using vismodegib, which was approved by the U.S. Food and Drug Administration in January 2012.
“The FDA approval is for locally aggressive basal cell carcinoma,” he said. “In our case, it is basal cell carcinoma that threatens the function of the eye or the lacrimal system.”
By taking the drug in its standard 150-mg dose, all of Kahana’s patients so far have had vision and the eye preserved. The drug is typically prescribed by an oncologist, and patients are managed by a multidisciplinary team.
“Fortunately, we have yet to encounter a patient who was unable to start the medication for health reasons,” Kahana said.
In Kahana’s early experience, there have been two kinds of responses to vismodegib. In about 25% of patients, the cancer remained stable and did not continue to grow, and in 75% of patients, the tumor regressed. In this latter population, some tumors have shrunk enough to be suitable for excision, without significant collateral damage to the eye, eyelids or drainage system.
“We have excised a shrunken tumor in a couple of patients so far, with good preservation of visual function,” Kahana said.
Published literature, though, indicates that some patients show no response to the drug, in which case the tumor continues to grow and requires the more traditional extensive surgery.
“We typically can assess whether there is a good response or not at between 3 and 6 months,” Kahana said. “Patients can continue the drug indefinitely, if they can tolerate it. Theoretically, the drug could be taken lifelong to shrink the tumor and keep the tumor at bay.”
The most common side effect of vismodegib is severe muscle spasms, which have affected at least 50% of Kahana’s patients, resulting in two or three patients discontinuing use. It is hoped that additional studies, such as the one being initiated by Kahana, will provide additional information on optimal use of this novel drug. – by Bob Kronemyer