Cell Therapeutics Inc announced that it has initiated an international phase I/II clinical trial of the novel polyglutamate-20S-camptothecin conjugate (CT-2106) in colorectal cancer patients. The open label study combines CT-2106 with infusional 5 fluorouracil/folinic acid (5-FU/FA) in patients with metastatic colorectal cancer who have failed front-line therapy with oxaliplatinum.

The first stage of the study will determine the maximum tolerated dose (MTD) of this combination, as well as the dose limiting toxicities, safety profile, and anti-tumor activity. Once the MTD has been determined, the study will progress to a second stage where CTI will evaluate the efficacy of the drug. A total of approximately 45 patients will be treated on the study.

"The preliminary phase I trial results of CT-2106 in advanced solid tumors provide a strong indication that the product may have the ability to substantially improve the toxicity profile of standard camptothecin as we observed that typical side effects, such as gastrointestinal and bladder toxicities, were notably absent," stated Jack W. Singer, M.D., chief medical officer of CTI. "Moreover, the results showed that CT-2106 retained the potent anti-tumor activity of this class of agents."

Camptothecins are one of the world's fastest growing classes of anti-cancer agents and are commonly used as treatment for colorectal, lung and ovarian cancer, however they are limited by severe side effects. The naturally occurring product, 20S-camptothecin is among the most potent compounds in this class of agents and was evaluated in phase I and II trials by the National Cancer Institute (NCI), but its development was discontinued due severe gastrointestinal and bladder toxicities which have not been seen with CT-2106 in phase I studies.

"To date, a total of 28 patients have been treated with CT-2106. The safety, pharmacokinetic and efficacy data from the phase I study will be presented at this year's ASCO meeting," said Singer. "Preliminary results have prompted our investment in advancing a broader phase II program in tumor types where camptothecins are known to be active, either alone or in combination with other agents. In addition to colorectal cancer, we plan to initiate international studies in small cell lung cancer and advanced ovarian cancer."

CT-2106 is the second agent in CTI's portfolio, after XYOTAX (paclitaxel poliglumex), to exploit the polyglutamate-conjugate technology, where an anti-cancer agent is conjugated to a naturally biodegradable poly-amino acid. The clinical experience with XYOTAX, which is completing enrollment in multiple phase III trials for non-small cell lung cancer, further confirms CTI's preclinical work, which has shown that the polyglutamate technology has the ability to eliminate the need for toxic solubilizing agents and decrease the amount of drug exposure in normal tissues while increasing the amount of drug reaching tumor tissues.