LEXINGTON, Mass.--(BUSINESS WIRE)--
Elesclomol is an investigational first-in-class oxidative stress inducer
that triggers apoptosis (programmed cell death) in cancer cells.
Elesclomol is being developed under a global collaboration agreement
As previously announced, Synta expects to complete enrollment of the
SYMMETRY trial in January or
SYMMETRY Trial Design
The SYMMETRY trial is enrolling patients with stage IV metastatic melanoma who have not received prior chemotherapy but who may have already been treated with non-chemotherapeutic agents such as biologics. Approximately 630 patients are being enrolled in the blinded, randomized, controlled study, which is being conducted at approximately 150 centers worldwide. Patients are randomized (1:1) to elesclomol (213 mg/m2) plus paclitaxel (80 mg/m2) or paclitaxel alone (80 mg/m2) and receive three weekly treatments and one week without treatment per each four week cycle. If tolerated, treatment continues until disease progression. Patients are stratified according to LDH levels, M-grade status and prior treatment history. Response is assessed using modified RECIST criteria at baseline and every eight weeks from the date of randomization, with radiology scans being assessed by independent, blinded, reviewers at a central site. The primary endpoint of the trial is progression-free survival (PFS); secondary endpoints include overall survival and response rate. No crossover is allowed from the paclitaxel control arm to the combination arm following disease progression, in order to facilitate the assessment of overall survival.
The control arm treatment, the combination arm treatment, the doses, the schedule, and the primary endpoint - PFS - are the same as in the prior, Phase 2b melanoma trial. The Phase 3 SYMMETRY trial design has been reviewed and agree to by the FDA under the Special Protocol Assessment process.
Elesclomol is an investigational first-in-class oxidative stress inducer that triggers apoptosis (programmed cell death) in cancer cells. Cancer cells operate at high levels of reactive oxygen species, or oxidative stress. Elesclomol acts by increasing the level of oxidative stress in cancer cells even further, beyond sustainable levels, inducing apoptosis. This mechanism of action, called oxidative stress induction, represents a novel way of selectively targeting and killing cancer cells.
In a double-blind, randomized, controlled Phase 2b clinical trial in 81 patients with stage IV metastatic melanoma, elesclomol in combination with paclitaxel met the primary endpoint, doubling the median time patients survived without their disease progressing, compared to paclitaxel alone (p = 0.035). The most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhea, and anemia.
A pivotal Phase 3 clinical trial of elesclomol in combination with paclitaxel in patients with stage IV metastatic melanoma (the SYMMETRYSM trial) is ongoing. Information about the SYMMETRY trial can be found at www.symmetrymelanomastudy.com, or www.clinicaltrials.gov, (NCI identifier # NCT00522834).
A Phase 1/2 trial of elesclomol in combination with docetaxel in patients with metastatic, hormone-refractory prostate cancer was initiated in 2008. Trials in other indications, and in combination with other agents, are planned.
Elesclomol has received Fast Track and Orphan Drug designation from the FDA for metastatic melanoma. The Phase 3 SYMMETRY trial design has been reviewed and agree to by the FDA under the Special Protocol Assessment process.
About Metastatic Melanoma
Melanoma, the most deadly form of skin cancer, arises from melanocytes,
the pigment-producing cells of the skin. According to the
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