Protoxin trial for recurrent prostate cancer
Protoxin, also called PRX302, is a drug being tested on men with localized recurrent prostate cancer in Phase I clinical trials in Texas and Vermont.
Patients considering this trial must have experienced recurrence after completing a full course of definitive external beam radiation or definitive brachytherapy (but not both) as primary therapy for diagnosed prostate cancer at least one year prior to enrollment
Our main news about Protoxin is here:
PSA-activated protoxin that kills prostate cancer: phase I clinical trial is underway
http://www.psa-rising.com/prostatecancer/protoxin1106.htm
A reader asked for a simpler, clearer explanation of what’s going on with this drug. Here’s what we know at the moment:
In Texas, one trial enrolled the first patients in May this year and is hoping to recruit 36 men with localized recurrent prostate cancer. Patients must have recurred after EBR or brachytherapy, have PSA level less than 20 ng/mL and PSA doubling time longer than 3 months. They must NOT be taking hormone drugs. Also, they must NOT have signs of metastatic disease including no bone metastases on bone scan, or any lymph node, lung, liver or soft tissue.
A link to info about that trial is here:
http://clinicaltrials.gov/ct/gui/show/NCT00379561?order=2
The 3 cancer centers so far are
1) Scott and White Cancer Center, Temple, Texas:
http://www.sw.org/sw/portal/_pagr/105/_pa.105/161
2) M. D. Anderson Cancer Center
3) University of Vermont (contact Dr. Mark Plante).
If you think you would want to be in this trial take this info to your doctor.
This Phase I trial aims to find out:
1) whether the drug is safe
2) whether it has side effects
3) whether it beats back the cancer.
So far they have reached the third “dose level” in testing the drug in the Temple, TX trial, which began in May and are moving forward to recruit more patients there and at the 2 other centers.
What they know so far is that PRX302 is activated (switched on) by PSA. It reduces the size of a prostate cancer tumor by destroying cancer cells. It does this by making a hole (or pore) in the cell membrane (the surface covering each prostate cancer cell).
PRX302 is injected into the prostate under ultrasound guidance.
PRX302 is expected to have fewer side effects than traditional or current systemic treatments because it is injected directly into the prostate.
The high level of PSA being produced by prostate cancer cells switches on the drug, the drug forms pores on the cell´s surface, and the cancer cells die.
This is the plan. Whether it will really work on men with localized recurrent prostate cancer, and whether it will keep working permanently or for a long time, no one will know for sure till the trial is further along and/or completed.
If it works reasonably well they will take it to a Phase II and then a Phase III clinical trial. Ultimately this might create a whole new treatment for men with early stage localized prostate cancer.
Another Phase I trial testing Protoxin for BPH (benign overgrowth of the prostate) is under way in Vancouver, Canada.
As I’m involved in this project, I’d like to clear up some errors in the above information
There are actually 4 sites: the fourth one is in San Antonio. Additional sites may be added soon.
The drug is called PSA-PAH1 (at least until a trade name can be assigned). The manufacturer is Protox Therapeutics in Vancouver. PRX302 is really just the protocol number.
It is a bio-engineered “pro-drug” that is converted by Prostate Specific Antigen (PSA)into a toxin that binds to and destroys PSA-producing cells in the prostate. In prostate cancer, it is hoped that this will reduce the tumor load. In BPH, it is hoped that this will shrink the gland and thereby relieve symptoms.
Comment by CancerResearcher — January 10, 2007 @ 3:28 amCancerResearcher, there are no errors in our report. Did you read the full story PSA-activated protoxin that kills prostate cancer: phase I clinical trial is underway
PRX302 is not “really just the protocol number.” It started out publicized by the company itself as an identifier assigned to this novel compound during testing from bench to clinical trials. The company’s website continues to use PRX302 as the name of the compound, e.g. in “Protox Therapeutics is currently conducting a Phase I clinical trial for patients with local recurrent prostate cancer using PRX302.”
Maybe the company muddled up the compound name and the clinical trials protocol identifier. That seems unlikely. But Clinicaltrials.gov, to which we link in our article, lists the trial under “Study ID Numbers: PRX302″ and lists the trial name as “PSA-Activated PSA-PAH1 for Locally Recurrent Prostate Cancer.”
Reporters who identify this protoxin as PRX302 are following the company and Sam Denmeade’s presentation at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Prague.
Patients who might be interested in this trial need to know the designation PRX302 so as to find this info on the web.
The bottom line is, this is a Phase I trial to evaluate safety and tolerability. Secondary aim is to track where this drug goes in the patient’s body, how long it stays there, whether it affects the immune system or has any other useful effects.
The compound has been tested on monkeys. The monkeys had been implanted with prostate cancer tumors. Presumably these monkeys did not have recurrent prostate cancer (unlike dogs, monkeys in the wild seldom develop prostate cancer). One day the monkey was healthy. The next day a researcher implanted a tumor in his prostate. Sometime soon after, the researcher injected the monkey’s tumor with PRX302. The researchers observed that the monkeys’ PSA’s fell. They killed the monkeys and autopsied them. They reported that the tumors had shrunk. Based on biopsy at autopsy and previous research in the lab in dish or test tube, the researchers say that when PRX302 came into contact with PSA, it punched holes in PSA-expressing cancer cells. Isn’t that how it went?
In the current trial the compound is injected into the prostates of men with biochemical recurrence (rising PSA) following primary therapy with external beam or radioactive seed implants. It’s expected that injection of the drug in the prostate will keep its effects localized.
Requirements for this Phase I trial include: “Patients must have recurred after EBR or brachytherapy, have PSA level less than 20 ng/mL and PSA doubling time longer than 3 months. They must NOT be taking hormone drugs. Also, they must NOT have signs of metastatic disease including no bone metastases on bone scan, or any lymph node, lung, liver or soft tissue.”
It remains to be seen, though, whether this drug might target PSA- expressing prostate cancer cells that are about to drift out into circulating blood or bone marrow. Some of those cells may be putting out some of the PSA that is signaling that these patients have recurred.
The trial blurb’s states that a secondary endpoint is “Immune response to PSA-PAH1.” This seems to suggest that the investigators expect the drug to perk up the patient’s immune system. If it should turn out, however, that some of the injected drug ends up targeting PSA in the blood, might this have the effect of depressing the immune system?
The trial outcomes and fate of patients in the trial are much more important than this quibbling over misleadingly changed names or designators.
Comment by admin — January 10, 2007 @ 5:56 pmWhy is this company using monkeys for their prostate cancer drug experiments? Find out more about research on monkeys. Is it worth it?
Animal rights groups blast support for monkey tests
JOHN VON RADOWITZ The Scotsman Dec 13 2006
http://news.scotsman.com/uk.cfm?id=1848612006
Bad Science: Using primates kills people
http://speakcampaigns.org/badscience.php/
Monkey Business
Comment by Tulli — January 11, 2007 @ 11:19 pmPrimates — destined for laboratory research — are being brought into a compound in Houston so carefully and quietly that no one knows they’re here
By Craig Malisow Aug 31, 2006
http://houstonpress.com/Issues/2006-08-31/news/feature.html
Why monkeys? The drug works by binding to PSA-producing cells, and only humans and higher primates produce PSA. The company only did one small study with monkeys and only because it was required by regulatory agencies to obtain permission to begin human trials. The company had to know what the drug does in a real prostate before they could expose humans to it. Unfortunately, there was no other way to get this critical information.
Comment by CancerResearcher — February 7, 2007 @ 5:47 pmWe all want to reduce or eliminate animal testing, but prostate cancer can be a deadly disease and this is a drug with the potential to save people’s lives!
The study eligibility requirements have been posted on CenterWatch.com:
Houston:
http://www.centerwatch.com/patient/studies/stu108306.html
San Antonio:
http://www.centerwatch.com/patient/studies/stu108308.html
Temple:
http://www.centerwatch.com/patient/studies/stu108304.html
Burlington:
http://www.centerwatch.com/patient/studies/stu108305.html
Also, the company has posted promising interim results:
Comment by CancerResearcher — February 7, 2007 @ 5:52 pmhttp://www.protoxtherapeutics.com/news/2007/011807.php
BTW, here’s another link…not to offend, but note herein that the study is called PRX302 by the lead investigator whereas the drug is called PSA-PAH1. They both seem to be used interchangably to describe the drug.
http://www.temple-telegram.com/story/2006/06/21/32452
Comment by CancerResearcher — February 7, 2007 @ 10:14 pmProtox Therapeutic’s PSA-PAH1 (or PRX302) is a pro-drug, meaning it is a drug that is inert until it is activated by a biochemical transformation within the body. It is basically a genetically-engineered toxin (hence the term pro-toxin) designed to be activated by PSA. It was originally derived from a bacterial toxin that was discovered and well-researched many years ago. The genetic sequence of the toxin was determined and then it was modified using gene-splicing techniques (to make it into a prodrug that is activated by PSA) before being cultured in a different bacterium. (Insulin and a lot of other famaliar drugs are made the same way!)
Because it is a protein molecule, the risk exists — as it does any time you put a non-human protein into a human — that there could be an allergic response. That is no different than any other “biologic”: Botox, for example is a similar toxin, except that Botox does not first have to be activated and thus Botox is not a protoxin and has no specificity for any certain tissue. Botox works by poisoning muscle cells; PSA-PAH1 works by poisoning PSA-producing prostate cells.
Bottom line, PSA-PAH1 (PRX302), is not designed to work systemically or to “improve the immune system”. The researchers are measuring systemic blood and urine levels just to make sure that it remains only in the prostate and doesn’t cause any systemic allergic (”immune system”) response. According to Protox Therapeutic’s last press release, there hasn’t been any systemic effects thus far (suggesting the drug’s effects are indeed restricted to the prostate). But, it remains an unanswered question. That is why clinical trials must be conducted (and why, unfortunately, animals studies are required as well)…to answer those kinds of questions before what looks to be a promising new drug is widely distributed.
Will PSA-PAH1 (or maybe a subsequent version) work on metastasized prostate cancer cells, say that have already spread to bone? It is too early to say. Unfortunately, that’s a question that will take a lot more research. Meanwhile, the company is trying to develop PSA-PAH1 for recurrent local prostate cancer and for benign prostatic hypertrophy (BPH). Let’s wish them great success!
Comment by CancerResearcher — February 7, 2007 @ 10:51 pm