The drug, known under the brand name Nanotax, is a fine particle reformulation of paclitaxel, the standard treatment for ovarian cancer. The drug was developed by Lawrence-based CritiTech, and the drug-testing and phase I clinical trial were conducted by KU Cancer Center researchers, led by Stephen Williamson, M.D., medical director of Cancer Clinical Trials.
Nanotax works by flipping the script on how paclitaxel is administered to patients and with how it鈥檚 formulated, potentially making it a more effective and better tolerated treatment for ovarian and other abdominal cancers.
During the trial, five out of 21 late-stage cancer patients survived more than 400 days after being treated with Nanotax at high concentrations for more than four weeks. Seventy four percent of enrolled patients were diagnosed with ovarian cancer with tumors that had relapsed and metastasized in the peritoneum, the membrane that lines the abdominal cavity. The treatment was well tolerated by patients and there were no serious adverse reactions reported from the drug.
The main purpose of phase I clinical trials are to evaluate the safety of a new drug, helping researchers determine the maximum dose that can be given safely as well as any harmful side effects. Patients enrolled in phase I trials can no longer be treated effectively with standard treatments.
Although the effectiveness of the new drug is not the main concern of a phase I trial, Dr. Williamson noted it was promising that five of the patients survived more than a year after starting the drug.
鈥淏ecause these patients have advanced disease, we didn鈥檛 think we鈥檇 see much benefit,鈥� said Dr. Williamson. 鈥淏ut some patients stayed on it for a longer period of time, which is more than what we expected and is promising.鈥�
Unlike regular paclitaxel, which is given intravenously over a few hours, Nanotax is given as a bolus injection, a single large dosage all at once. It鈥檚 injected directly into the peritoneum through a catheter, which exposes the tumors to higher concentrations of the drug compared to standard IV paclitaxel treatment.
鈥淭he fine particles of this drug allow for it to be released slowly and stay in the abdomen,鈥� said Katherine Roby, Ph.D., research associate professor in the Department of Anatomy and Cell Biology at KU Medical Cancer, who started her pre-clinical work on Nanotax more than a decade ago. 鈥淭he concentration of the drug stays higher in the space where the cancer is, killing more cancer cells. This allows less of the drug to be absorbed systemically and fewer side effects.鈥�
Previous studies on mice showed that Nanotax had a ten-fold higher maximum tolerated dose compared to paclitaxel. It also increased overall survival compared to paclitaxel.
The lack of major side effects is also a good sign for future usage of Nanotax. When regular paclitaxel is given to patients, it is mixed with ethanol and castor oil derivative, and many patients develop an allergy to that additive (all patients are pretreated to prevent serious allergic reactions). Nanotax is the fine particle formulation of paclitaxel mixed with saline, which the body can absorb and tolerate much better without the allergy risk.
鈥淭he significance of this trial is that many patients鈥� develop an allergy to what is mixed with paclitaxel, creating more side effects,鈥� said Dr. Williamson. 鈥淭his new drug eliminates those side effects because it stays in its pure form and doesn鈥檛 need the problematic agent mixed with it.鈥�
Because Nanotax is a repurposed form of an already in-use drug, it shortened the time between animal and patient trials. If the drug makes it through subsequent patient trials, it will be available for doctors to prescribe much sooner than a drug created from scratch. The time it takes for a new drug to go from bench to prescription pad can be staggering鈥攖ypically three to six years are needed for development before it鈥檚 even ready for safety and efficacy testing, according to the Pharmaceutical Research and Manufacturers of America.
CritiTech will be working with the U.S. Food and Drug Administration when it comes to the next phases of testing and developing Nanotax.
鈥淲e may be testing this drug in combination with others in the next phase of trials,鈥� said Dr. Williamson. 鈥淚t does make it easier to get to patients sooner since paclitaxel is already on the market and we know a lot about how it works.鈥漁varian cancer is difficult to treat because it鈥檚 not often diagnosed until it has already metastasized to the peritoneum, liver or lung, the most common sites of metastasis according to the National Cancer Institute. Sixty one percent of ovarian cancers have already metastasized at diagnosis, according to the National Cancer Institute. About 44.6 percent of patients survive five years after being diagnosed. Other cancers that can metastasize to the peritoneum include pancreatic, colorectal, liver and bladder cancers.
鈥淯ltimately, everyone is hoping it will be a first line of treatment for these types of abdominal cancers,鈥� said Dr. Roby. 鈥淎nd from the results of this phase I trial, it should clear the way for the drug to move forward in that direction.鈥�
Other KU Cancer Center faculty involved in Nanotax trial:
Gregory Reed, Ph.D, associate professor of pharmacology, toxicology and therapeuticsJulia Chapman, M.D., FACOG, associate professor of obstetrics and gynecologyGary Johnson, M.D., FACOG, professor of obstetrics and gynecology
Other clinical trial sites:
Cancer Center of Kansas (Wichita)Peggy & Charles Stephenson Oklahoma Cancer Center (Oklahoma City, OK)
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