New Phase III trial of “gene suicide therapy” in localized prostate cancer

A biopharmaceutical company called Advantagene, Inc. announced last Thursday that it has reached agreement with the U.S. Food and Drug Administration regarding the conduct of a Phase III clinical trial of a vaccine-like treatment called ProstAtak™ — in combination with standard therapy — in the treatment of patients with newly diagnosed prostate cancer.

According to the company’s media release, and other information on the company’s web site, ProstAtak uses what the company is calling “gene-mediated cytotoxic immunotherapy” (GMCI™) to assist in the prevention of recurrence of localized prostate cancer in men being treated with standard forms of therapy. Some earlier literature refers to this type of treatment as “suicide gene therapy” (see Cher et al.). The proposed Phase III trial is expected to start accruing patients later this year. The projected number of men to be accrued to the trial is 711, and the company says that definitive trial results should be available by 2015.

There is no specific information in the press release, but the proposed trial would be randomized and double blind, with about 470 patients receiving ProstAtak and the other 241 being treated with a placebo. The further implication of the announcement is that Advantagene and the US FDA have been able to come to agreement over a set of endpoints for the trial that would define prostate cancer recurrence after first-line treatment.

The precise details of the ProstAtak treatment are not clearly spelled out either in the company’s press release or in other information on the company’s web site. What we can tell readers at present is that ProstAtak  is a combination of a biologic vector known as AdV-tk (adenovirus thymidine kinase) and the drug valacyclovir (aka Valtrex). According to the the media release,  ‘ProstAtak™ is designed as an “off-the-shelf” drug to kill tumor cells and stimulate a vaccine effect against the patient’s specific tumor, in essence activating the patient’s own immune system to prevent tumor recurrence.’ We get the impression that the trial would require three or perhaps four cycles of treatment with the combination of AdV-tk + valacyclovir. Adverse effects associated with this combination of therapies are not yet clearly defined in the published literature (but see the two annual meeting abstracts referred to below).

There is no information about this trial yet on the web site. Presumably such information will be forthcoming withing the next couple of months. However, an article by Aguilar et al. was published in April this year and gives further information about the premise behind the clinical development of ProstAtak. Interim results of a Phase I/II clinical trial were reported by Aguilar et al. at the annual meeting of the American Society of Clinical Oncology back in 2002 with subsequent, follow-up data in 2004.

One should be able to gain some degree of confidence about the quality of the proposed trial by knowing that the two people who chaired the committee that designed the protocol were  Dr. Peter Scardino, Chief of Surgery and Chair of Urology at Memorial Sloan-Kettering Cancer Center and Dr. Theodore DeWeese, Chair of Radiation Oncology at Johns Hopkins. According to Dr. Scardino, “We are delighted to lead this study. I participated in early trials with this product, and am enthusiastic that this randomized trial will definitively evaluate its potential.”

We would note that other forms of vaccine-like therapy have, in the not so distant past, also been investigated for their potential to prevent progression of localized prostate cancer — the most recent being GVAX. To date, there has been no drug or biotherapeutic that has ever demonstrated the ability to prevent progression of localized prostate cancer when used alone or as an adjuvant to standard forms of therapy.

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