Nuvilex reports combined results of the initial Phase 1/2 clinical trial and second Phase 2 clinical trial of Cell-in-a-Box

The title of the publication is "Encapsulated Cells Expressing a Chemotherapeutic Activating Enzyme Allow the Targeting of Subtoxic Chemotherapy and Are Safe and Efficacious: Data from Two Clinical Trials in Pancreatic Cancer." The entire report can be viewed by clicking http://www.mdpi.com/1999-4923/6/3/447 and then clicking on "Full-Text PDF" on the left side of the page.

Nuvilex’s CEO and President, Kenneth L. Waggoner, commented, "It is very interesting to see the results of a second Phase 2 clinical trial of our pancreatic cancer treatment in patients with advanced, inoperable pancreatic cancer compared and contrasted to the results of the initial Phase 1/2 clinical trials, with the results from both summarized together in this single publication.

"We believe the results from the second Phase 2 clinical trial show that the efficacious nature of Nuvilex’s pancreatic cancer treatment seen in the Phase 1/2 trial was once again evident in the Phase 2 clinical trial. However, discrepancies between the two trials are also reported. For example, in the second Phase 2 clinical trial, when the dose of ifosfamide was increased over that used in the Phase 1/2 clinical trial, the antitumor effectiveness of the treatment appeared to be slightly reduced, but the side effect profile of the treatment was increased in severity.

"Also, we believe that the overall utility of Nuvilex’s pancreatic cancer treatment was illustrated by the fact that it could be readily employed in multiple treatment centers. Interestingly, noted European gastroenterologist and oncologist Dr. Matthias Lohr was Principal Investigator for both clinical trials. Dr. Lohr is assisting Nuvilex in the development and oversight of our upcoming Phase 2b clinical trial in Australia."

In total, 27 patients with advanced, inoperable pancreatic cancer have been treated with the Cell-in-a-Box(R)/ifosfamide combination – 14 in the Phase 1/2 clinical trial and 13 in the second Phase 2 clinical trial. Both trials were uncontrolled (no comparator arms), open-label studies.

In each of the clinical trials, a single implantation of Cell-in-Box(R) capsules (each capsule contained approximately 10,000 cells capable of converting the anticancer prodrug ifosfamide into its "cancer-killing" form by virtue of their over-expression of an isoform [CYP2B1] of human cytochrome P450) was used and two courses of treatment with ifosfamide were administered. In both clinical trials, there were no deleterious effects, such as inflammation or pancreatitis, that could be attributed to the Cell-in-a-Box(R) capsules being implanted in the patients.

The median survival of patients in the Phase 1/2 clinical trial was about 40 weeks versus the 33 weeks seen in the Phase 2 clinical trial. The percentage of patients who survived one year was somewhat lower in the Phase 2 clinical trial (23%) than in the Phase 1/2 clinical trial (38%).

There were several other differences between the trials. First, whereas the Phase 1/2 clinical trial was done at a single study center (in Rostock, Germany), the Phase 2 clinical trial was conducted at four centers in two European countries (in Rostock, Berlin and Munich in Germany, and in Berne, Switzerland).

Second, the dose (1 g/m2) of ifosfamide used in the Phase 1/2 clinical trial was one-third of the "normal" dose of ifosfamide, whereas the dose used in the Phase 2 clinical trial was twice (2 g/m2) that dose. Third, differences were seen in the severity of adverse events (side effects) in the two clinical trials. In the Phase 1/2 clinical trial, no adverse events were seen that could be attributed to the treatment, but in the Phase 2 clinical trial, severe side effects were observed that the investigators believed were caused by the higher dose of ifosfamide used in the latter trial.

According to a quality-of-life (QOL) questionnaire, although a reduction in the severity of the pain associated with the disease was noted in both studies, other deleterious effects on QOL were reported by patients in the Phase 2 clinical trial that were not reported by patients in the Phase 1/2 clinical trial. In light of these results, we believe that 1 g/m2 rather than 2 mg/m2 is the appropriate dose of ifosfamide to use as part of Nuvilex’s treatment for advanced, inoperable pancreatic cancer.

Mr. Waggoner concluded, "With the publication of this article in Pharmaceutics, the history to date of the development of Nuvilex’s pancreatic cancer treatment has been completed. The ‘rest of the story’ is now being written, beginning with the preclinical studies by Translational Drug Development (TD2) set to commence in the U.S. during the week of August 18, 2014. These initial preclinical studies will examine the effects of our cancer treatment on the rate of accumulation of malignant ascites fluid. A subsequent study to be conducted by TD2 will concern the effects of our treatment on the severe pain associated with pancreatic cancer. Nuvilex’s two-prong approach to the treatment of advanced, inoperable pancreatic cancer will be rounded out with our Phase 2b clinical trial to be conducted in Australia under the aegis of our Clinical Research Organization in that country, Clinical Network Services."