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Potential Therapies for HRPC
Evaluations of Drugs
and Treatments That are not yet FDA-approved for HRPC and Clinical Trial
Information
TABLE OF CONTENTS
Introduction
Clinical Trial Resources - This covers
Access to Investigational Drugs (Compassionate Use, expanded use, etc.).
Find there also, background on clinical trials, clinical trial consortiums, and
finding a clinical trial. There is also links to pages devoted to the personal
experiences of patients in various clinical trials.
Some specific drugs of interest to HRPC patients:
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Alpharadin (this is a link to the
manufacturer's website) - a new radiopharmaceutical Radium 223 and emits alpha
particles (helium nuclei) as opposed to the beta particle emitters like
samarium or strontium. Currently in phase II testing. Alpharadin is
being developed for skeletal metastases in patients with late-stage, HRPC.
Algeta is expecting to progress Alpharadin to pivotal Phase III clinical
studies in 2008 based on positive Phase II data, which show that it delays the
progress of prostate cancer and reduces the extent and effect of metastasis.
An 11 December 2009 press release from Algeta announced the first USA phase
III study at Tulane Cancer Center, New Orleans with Oliver Sartor, MD as the
principal investigator. This is a randomized trial and enrollment has
recently begun. The ALSYMPCA (ALpharadin in SYMptomatic Prostate
CAncer) study is a double-blind, randomized, controlled trial that enrolls
patients with CRPC and symptomatic bone metastases who will be randomized to
receive Alpharadin (radium-223 chloride) plus best standard of care or
placebo plus best standard of care. Approximately 750 patients are expected
to be enrolled at more than 125 medical centers worldwide. Algeta expects to
enroll patients across up to 15 sites in the US. Global recruitment remains
on schedule and is expected to be complete by the second half of 2010. The
estimated trial primary completion date is targeted as October 2012
(final
data collection date for primary outcome measure) which is survival.
Completion date for the trial is stated to be December 2013.
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Apatone
(HE3235), this drug has been through
phase I and II. It might be useful as a 2nd line treatment following first
line HT. It's primary use may be for extending the off time from
chemotherapy (pill form) or in an IV form as a drug that would augment
chemotherapy. Apatone is a combination of vitamin C and vitamin K3.
The phase II results have been published and are available free.
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ASA404 (DMXAA). DMXAA represents a new class of drugs that are
tumor-vascular disrupting agents(ASA404, vadimezan,
5,6-dimethylxanthenone-4-acetic acid/DMXAA).
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Atrasentan
(ABT – 627) Phase III clinical trials are running to evaluate this
drug that may delay progression of bone metastases and reduce pain. The new name
is Xinlay™.
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Cabazitaxel. This ≥ 2nd line chemotherapy candidate
is now approved by the FDA. There is now a webpage that is devoted to
cabazitaxel.
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COX-2 Inhibitors(and
NSAIDS). Off-label use.
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Sulindac (clinoril)
This is a possible interim approach while the drug Aptosyn finishes clinical
trials and gets FDA approval. Off-label use.
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Exisulind(Aptosyn).
Development of this drug has likely been discontinued.
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IMC-A12.
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Ipilimumab. Also called MDX-010 or MDX-101. It is a human monoclonal
antibody being developed by Bristol-Myers Squibb and Medarex. It is intended
to be used as a drug to activate the immune system. Wikipedia explains, "Ipilimumab
is a fully human antibody that binds to CTLA-4 (cytotoxic T
lymphocyte-associated antigen 4), a molecule on T-cells that is believed to
play a critical role in regulating natural immune responses. The absence or
presence of CTLA-4 can augment or suppress the immune system's T-cell
response in fighting disease. Ipilimumab is designed to block the activity
of CTLA-4, thereby sustaining an active immune response in its attack on
cancer cells."
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Ixempra (Ixabepilone).
This
is a Bristol-Myers-Squibb chemotherapy drug approved for advanced breast cancer
and being tested in HRPC patients. It is a semi-synthetic analog of Epothilone B. The
epothilones are a class of non-taxane microtubule-stabilizing agents. Bill Aishman
wrote a paper in 2003 about this drug's development - before the results of
various HRPC clinical trials were published, see "Epothilone B, A New, Effective
Chemotherapy Drug for Advanced Prostate Cancer in Our Lifetime?"
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MDV3100, a small-molecule androgen
receptor antagonist that inhibits androgen receptor function by blocking
nuclear translocation of the androgen receptor and DNA binding, currently in
phase I/II testing. There is an article on Medscape covering
results of phase I/II
as of October 2008. A phase III trial is now recruiting patients
(January 22, 2010). Called AFFIRM (A Study Evaluating the EFFicacy and
Safety of Investigational DRug MDV3100 in Men with Advanced Prostate
Cancer),
The Affirm Trial is a Phase 3 (late-stage) clinical research trial that will
include about 1200
participants. The trial will test the effects of an oral investigational
drug called MDV3100 in men
with advanced prostate cancer that continues to progress despite treatment
with chemotherapy and
hormone therapy. The purpose of the Affirm Trial is to determine whether
MDV3100 can safely slow the progression of the disease and extend the lives
of men with prostate cancer. See www.affirmtrial.com and a
flyer is
also available.
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MoAbs -
A Personal Experience With a Targeted
Chemotherapy Clinical Trial
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Noscapine - This is an over-the-counter
cough suppressant that has show in vivo that it is an
anti-PCa agent.
The PCREF organization is working to bring this into testing with patients (see
the Noscapine website). 7 March 2007.
PSA-Rising has some current (12/2008) information on noscapine.
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Phenoxodiol, a synthetic anticancer drug analog
of genestein currently being tested for ovarian cancer. There has been one
trial in HRPC patients that showed lots of promise.
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Quadramet
(Samarium) with a Vaccine. The official title of this phase 2.5 clinical trial
is: "A
Randomized Phase 2.5 Study of 153Sm-EDTMP (Quadramet) With or Without a
PSA/TRICOM Vaccine in Men With Androgen-Insensitive Metastatic Prostate Cancer
NCI-07-C-0106." The rationale for this combination is
that the PROSTVAC-V/TRICOM vaccine has been shown to be safe and to have some
preliminary activity plus there have been pre-clinical studies suggesting that
there is synergy between Quadramet and immunotherapy (see abstract #4398, 97th
AACR Annual Meeting, April 1-5, 2006.). Prior taxotere use allowed. Bone
metastases required, but no soft tissue disease.
Arm I:
Patients receive 153Sm-EDTMP IV over one minute on Day 8
Treatment with 153Sm-EDTMP will be repeated every 12 weeks if there is
adequate hematologic recovery
Arm II:
Patients receive PROSTAC-V/TRICOM (vaccine) subcutaneously on Day 1
Patients receive 153Sm-EDTMP IV over one minute on Day 8
Treatment with 153Sm-EDTMP will be repeated every 12 weeks if there is
adequate hematologic recovery
Patients receive PROSTVAC-F/TRICOM (fowlpox) subcutaneously on Days 15, 29,
and then every 4 weeks
Patients receive sargramostim (GM-CSF) subcutaneously daily for 4 consecutive
days, beginning the day of each PROSTVAC vaccination
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Satraplatin(JM-216).
Withdrawn, failed phase III Sparc - median survival no better than prednisone
alone. Satraplatin is being developed as a second-line chemotherapy for HRPC
patients. See the news release from 23 February 2007, entitled, "Satraplatin
Shown to Significantly Reduce Risk of Disease Progression in Advanced
Hormone-Refractory Prostate Cancer Patients."
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TAK-700. This is a nonsteroidal
inhibitor of the 17,20-lyase enzyme to treat HRPC disease.
Pre-clinical results: TAK-700 binds to and inhibits 17,20 - lyase in
both the testes and
adrenal glands.
Phase I. 26 patients, dose of 300 mg 2x/day was well tolerated in
patients with metastatic HRPC
Phase II. Enrollment is ongoing.
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Vaccines, includes a personal account of the Provenge vaccine trial.
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Valproic Acid (Depakote ER). This drug is
available "off label" for HRPC. Its use for HRPC isn't proven yet.
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Velcade. Velcade
was also known as PS-341, MLN341 and LDP-341. It's generic designation is "Bortezomib"
and it is a proteasome inhibitor. This paper, by Bill Aishman, is entitled, "Velcade:
the Magic Bullet for Cancer?"
For a list of "emerging therapies"
and some information about them, visit the Us Too website page at
http://www.ustoo.org/Emerging_Treatments.asp
In this section we present our evaluations of various new and old therapies that may have some effect on
HRPC. Keep in mind that we are not doctors—just patients who do our homework. We are trying to provide rational options that you can review with your oncologist.
We identify some of these therapies through our internet contacts and some through media announcements. It is our belief that there are also some answers out there in the medical literature that—for whatever reason—are not being pushed by the medical community or the pharmaceuticals. By sorting out these therapies we hope to help our medical teams by providing workable ideas for consideration.
Since there is some urgency to our search, we have established criteria that are meaningful to us as people living with
HRPC:
Is there hard evidence that this therapy has beneficial effects for humans with
HRPC? We consider evidence to be published clinical studies in the recognized medical literature. Or it may be documented anecdotal evidence by people with no financial stake in the product. Pre-clinical studies (in vitro and in vivo with mice) rarely translate to successful drugs and even more rarely in fewer than 10 years.
Is there hard evidence that this drug will not harm or kill the user? Simply put, if this one doesn’t work, will I survive to continue my fight?
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Is this drug available now (or within 12 months) for use? Tough question. But, if you can’t get it, it’s of no value in your fight against
HRPC. However, it may be available in a trial or under compassionate use, so don’t write off a good prospect without trying.
Using these criteria, we have tried to provide a meaningful evaluation of new therapies so that you have the basis for a discussion of potential therapies with your oncologist. Each evaluation is reported in a similar format to help you compare alternatives.
None of us has any stake, financial or otherwise, in any of these therapies. We are all simply looking for the best answers available today for
HRPC.
If you learn something of value as a result of using these evaluations, we will appreciate hearing from you so that we can continue to build this database of knowledge for everyone’s use.
Updated 8/6/2008
Howard Hansen
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