NeoPharm's phase 3 trial of cintredekin besudotox for brain cancer achieves patient enrollment

By E. Janene Geiss

Philadelphia, Dec. 9 - NeoPharm, Inc. announced Friday that its cintredekin besudotox (IL13-PE38QQR) pivotal phase 3 Precise trial for the treatment of Glioblastoma Multiforme (GBM), the most aggressive form of brain cancer, has achieved the 270 intent-to-treat patient enrollment milestone.

As previously reported, the Precise trial protocol allows for enrollment of up to 300 patients in order to obtain 270 patients with confirmed GBM at first recurrence at study entry surgical resection, for the intent-to-treat patient population, according to a company news release.

Only 288 patients were required to be enrolled to meet the 270 intent-to-treat patient population, officials said.

"Patient enrollment was achieved within the expectations of a year-end 2005 enrollment target. I believe that this is a good indication of the high level of expertise and diligence we were able to obtain with the sites selected for this important clinical trial, and the strength of the controls designed by us for the execution of the trial," Guillermo A. Herrera, NeoPharm's president and chief executive officer, said in the release.

The company reported in November that it had been notified by the independent Data Monitoring Committee for the Precise trial that the study had reached the criterion for the second futility analysis (100 deaths). The company said it is awaiting the committee's analysis of the data and its recommendation, currently expected to be received by the end of the month.

Based on its review, the committee can recommend that the trial continue per the approved protocol, the trial continue with an additional 75 patients to account for data variability or the trial should end, officials said.

Even in the event of a recommendation to increase the number of patients in the trial, the interim efficacy statistical analysis for the trial would continue to be triggered at 160 deaths, with final efficacy at 215 deaths, as per the company's amended Special Protocol Assessment, setting up the potential for a Biologic License Application filing as early as the second half of 2006 if results meet requirements, officials said.

In accordance with the trial's protocol, having obtained 270 patients with confirmed GBM at first recurrence, further screening of patients will be suspended pending the decision of the committee as to whether or not additional patients will need to be enrolled, officials said.

Additional patients already randomized, or in the screening process, at the time the company achieved the 270 intent-to-treat patient milestone will be allowed to proceed in the trial if they meet all other entrance criteria, officials said.

Cintredekin besudotox (IL13-PE38QQR) is a recombinant protein composed of two parts: a tumor-targeting molecule and a cytotoxic agent. The drug is delivered via Convection Enhanced Delivery, a novel drug-delivery system using catheters placed following tumor resection in areas with microscopic tumor spread or at risk of tumor spread around the tumor resection cavity, officials said.

IL13 receptors are present in appreciable numbers on malignant glioma cells, but only to a minimal amount if at all on healthy brain cells. The IL13 portion binds to receptors on tumor cells like a key fits into a lock. The cancer cell latches onto and absorbs the IL13 and the attached PE, causing destruction of the cancer cell. Healthy brain cells appear to be unharmed because they do not internalize the PE, officials said.

Promising data for this potential therapeutic advance in the treatment of GBM was observed in phase 1/ 2 studies. The importance of adequate catheter positioning in order to achieve optimal distribution of cintredekin besudotox in brain tissue was assessed, leading to the specific guidelines for catheter positioning and deferred catheter placement used in the Precise trial, officials said.

Cintredekin besudotox has received orphan-drug designation in Europe and the United States and fast-track drug development program status from the Food and Drug Administration.

NeoPharm's cintredekin besudotox development program was also selected to participate in the FDA Continuous Marketing Application Pilot 2 Program.

NeoPharm, based in Lake Forest, Ill., is a biopharmaceutical company focused on research, development and commercialization of cancer drugs.

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