Cell Therapeutics, Inc. and the Data Safety Monitoring Board (DSMB) have agreed to close the PGT305 Pioneer lung cancer clinical trial and take patients off both treatment arms.
CTI's decision was due, in part, to the utility of the current trial given its plans to submit a new protocol to the US Food and Drug Administration (FDA) and in light of the aberrantly low rate of deaths in the control group. CTI plans to submit a new protocol by the end of the year, under a Special Protocol Assessment, to the FDA.
The new protocol, PGT306, will focus exclusively on women with normal estrogen levels, the subset where Xyotax has demonstrated the greatest survival advantage in the Stellar trials.
"While the patients in the Pioneer PGT305 study will not count toward our final pivotal trial results, the data from this trial will be instrumental in helping us understand the unique properties of this biologically enhanced chemotherapeutic and its potential as a gender specific therapy for women with lung cancer and other tumours where estrogen can influence the uptake and metabolism of Xyotax," said CTI President and CEO, James A. Bianco, M.D.
Xyotax (paclitaxel poliglumex) is a biologically enhanced chemotherapeutic that links paclitaxel, the active ingredient in Taxol, to a biodegradable polyglutamate polymer, which results in a new chemical entity. When bound to the polymer, the chemotherapy is rendered inactive, potentially sparing normal tissue's exposure to high levels of unbound, active chemotherapy and its associated toxicities. Blood vessels in tumour tissue, unlike blood vessels in normal tissue, are porous to molecules like polyglutamate. Based on preclinical studies, it appears that Xyotax is preferentially distributed to tumours due to their leaky blood vessels and trapped in the tumour bed allowing significantly more of the dose of chemotherapy to localize in the tumour than with standard paclitaxel. Once inside the tumour cell, enzymes metabolize the protein polymer, releasing the paclitaxel chemotherapy. Preclinical and clinical studies support that Xyotax metabolism by lung cancer cells may be influenced by estrogen, which could lead to enhanced release of paclitaxel and efficacy in women with lung cancer compared to standard therapies.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.