A partial halt has been put on the phase 3 ENLIVEN study, which is investigating the use of the novel oral CSF-1R inhibitor pexidartinib (PLX3397) in the treatment of tenosynovial giant cell tumor (TGCT). This trial has stopped enrollment of new patients on the recommendation of the data monitoring committee after a review of safety issues.
The trial will proceed with currently enrolled patients under a revised protocol.
Daiichi Sankyo, the company developing PLX3397, said in a release that the decision to halt enrollment comes after a review of recently reported cases of nonfatal, serious liver toxicity.
At the time of enrollment suspension, 121 patients had been enrolled, which was just five short of the 126 that had been planned for full enrollment.
The data monitoring committee has recommended measures that will address these safety concerns while maintaining the blinded nature of the study.
"The ENLIVEN protocol has been amended to add more frequent liver monitoring as well as additional tests," Jennifer Brennan, a spokesperson for Daiichi Sankyo, told Medscape Medical News. "More data analyses will be performed, and new monitoring measures may be taken accordingly."
TGCT, also known as pigmented villonodular synovitis or giant cell tumor of the tendon sheath, is a rare tumor that affects the synovium-lined joints, bursae, and tendon sheaths. It causes swelling, pain, stiffness, and reduced mobility in the affected joint or limb.
Although it is technically not considered a malignancy because it generally does not metastasize, it is nevertheless an extremely destructive tumor that often recurs after initial surgical treatment.
Therapeutic options are limited. The primary treatment of TGCT includes surgery to remove the tumor, but in patients with a diffuse form, it can wrap around bone, tendons, ligaments, and other parts of the joint. This makes the tumor difficult to remove, and multiple surgeries or joint replacement may be required. It may eventually advance to the point where amputation needs to be considered.
Recurrence rates range from 15% to 45%, according to Daiichi Sankyo.
As previously reported by Medscape Medical News, last year, findings from a phase 1 trial in 23 patients showed promising results with pexidartinib.
In that trial, treatment yielded a partial response in 12 of 23 patients and stable disease in seven patients, for an overall response rate of 52% and a disease control rate of 83%. Responses usually occurred within the first 4 months of treatment. The median duration of response exceeded 8 months, according to the study authors.
"We saw patients who were very symptomatic often show a remarkable improvement in symptoms very rapidly," said lead author William Tap, MD, chief of the sarcoma medical oncology service at Memorial Sloan Kettering Cancer Center in New York City, at the time the study was published.
In some patients, he noted that "these tumors seem to melt away."
The product is also being investigated for the treatment of glioblastoma, melanoma, and breast cancer, as well as in combination with the anti-PD-1 therapy pembrolizumab (Keytruda, Merck & Co.) for advanced melanoma and other multiple solid tumors.
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Cite this: ENLIVEN Study in TGCT Halts Enrollment Due to Safety - Medscape - Oct 26, 2016.
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