Marshall Edwards, Inc. Expedites Pivitol Trial for Phenoxodiol in Women With Chemo-Resistant Ovarian Cancer; Leading Global Clin
March 07 2005 - 8:30AM
PR Newswire (US)
Marshall Edwards, Inc. Expedites Pivitol Trial for Phenoxodiol in
Women With Chemo-Resistant Ovarian Cancer; Leading Global Clinical
Research Organization Selected to Manage Phase III Multinational
Ovarian Cancer Trial STAMFORD, Conn., March 7
/PRNewswire-FirstCall/ -- Marshall Edwards, Inc. (Nasdaq: MSHL;
LSE-AIM: MSH) has appointed a major international Clinical Research
Organization (CRO) to project manage the final stages of the
clinical program of the experimental anti-cancer drug, phenoxodiol.
The CRO will manage a new trial that seeks to produce data suitable
for an application seeking marketing approval in the USA and
elsewhere for phenoxodiol for the treatment of recurrent,
chemo-refractory ovarian cancer. This pivotal trial will be known
as the OVATURE trial. Patients interested in further information
are asked to visit http://www.phenoxodiol.com/ for trial updates.
"This pivotal study has been expedited in a departure from the
normal progression of clinical development, as a result of the
findings from the current Phase Ib/IIa trial," said Dr. Graham
Kelly, Executive Chairman, Marshall Edwards, Inc. "Although the
Phase IIa study is not fully enrolled, the positive tumor responses
in that study have convinced the Company to move forward without
delay into a pivotal trial." Phenoxodiol is being developed as a
drug that has anti-cancer activity in its own right, but also has a
particular clinical benefit in being able to restore sensitivity to
standard drugs in patients with cancer that has become unresponsive
to such drugs. Ovarian, prostate and renal cancers are three such
cancer types where phenoxodiol is being developed as a
chemo-sensitizer. In the case of patients with late-stage ovarian
cancer, the development of resistance to standard drugs is a major
barrier to the successful management of these cancers. Being able
to restore sensitivity to platinum drugs in particular would
represent a major breakthrough in the management of such cancers.
This pivotal study represents the third and final stage in the
development of phenoxodiol for this indication. In the first stage
(Phase Ib), 40 women with recurrent ovarian cancer were treated
with the intravenous dosage form of phenoxodiol alone. That study
confirmed the safety and tolerability of phenoxodiol, and
identified a suitable dose to take into the next study. The second
study (Phase Ib/IIa) had the objective of confirming the ability of
phenoxodiol to restore the sensitivity of late-stage ovarian
cancers to the two standard first-line chemotherapies in ovarian
cancer. The women enrolled in this study had tumors that were
resistant or refractory to platinums and /or taxanes, a situation
where further response to any therapy is low and any response to
platinum or taxane therapy is highly unlikely. This study is
ongoing with 43 women enrolled out of a planned 60 patients. This
trial includes a control arm where women are being re-challenged
with a platinum drug or with paclitaxel in the most stringent
manner possible to confirm a refractory state before being given
combination therapy. This ongoing study has produced radiographic
data showing tumor response which formed the basis of the US Food
and Drug Administration (FDA) granting phenoxodiol Fast Track
status in November 2004 for its intended use as a chemo-sensitizing
agent in late-stage, recurrent, refractory ovarian cancer.
Accordingly, the potential of phenoxodiol to be used as a
chemo-sensitizer has been confirmed. The proposed pivotal study to
be externally managed by a major international Clinical Research
Organization will be run in three stages and will involve clinical
sites in Australia, UK and the USA. The first two stages (Phase IIb
and Phase IIIa) are continuous. The Phase IIb study will compare
the oral and intravenous dosage forms of phenoxodiol in up to 100
patients. The Phase IIIa study will use the preferred dosage form
and will accrue sufficient patients to support an application to
the FDA for drug marketing approval. Although patients will be
recruited who are categorized as being refractory, patients will be
re-challenged to confirm their refractoriness, which will provide
the ultimate level of stringency for determination of chemical
resistance. Only those patients showing disease progression on
their prior chemotherapy will be accepted into the study and
treated with phenoxodiol plus their former chemotherapy drug. The
critical endpoints will be tumor response as indicated by
measurement of tumor size, the levels of the tumor marker C125, and
the time to disease progression. If marketing approval is received
at this point, then a third stage (a Phase IIIb study) will be
conducted in order to demonstrate an overall increase in patient
survival. About Ovarian cancer Ovarian cancer is the most lethal
gynecological malignancy, and the fifth leading cause of cancer
related death in women in the United States. The American Cancer
Society estimates that there will be about 22,220 new cases of
ovarian cancer in this country in 2005. About 16,210 women will die
of the disease. One in 70 women will develop ovarian cancer and one
out of 100 women will die from this disease. This high mortality is
due mainly to the inability to detect early disease, with
approximately 80% of patients being diagnosed in advanced-staged
disease. However, even in those patients diagnosed with early-stage
disease, the five-year survival rate ranges from 60 to 90%
depending on the degree of tumor differentiation. The standard
first-line treatment of ovarian cancer is a platinum drug
(cisplatin or carboplatin) used alone or coupled with a taxane
(paclitaxel). In patients with advanced disease, 80%-90% will
respond to such first-line chemotherapy. Of patients who respond to
first-line chemotherapy, less than 10 - 15% of these will remain in
remission, and most relapsed cases are chemo-resistant, showing
little if any further sensitivity to platinums or taxanes. Drugs
such as gemcitabine, doxorubicin and topotecan are used commonly in
subsequent lines of chemotherapy, but the development of
chemo-resistance to first-line drugs extends in large measure also
to these other drugs. The failure of some ovarian cancers to
respond to first-line chemotherapy (chemo-insensitivity) and the
development of resistance to multi-drug therapies
(chemo-resistance) represent the major hurdles to effective therapy
of ovarian cancer. There is an urgent need to devise strategies
that will both improve the response rate and degree of response to
chemotoxic drugs in the first instance, and/or will restore
chemo-sensitivity in late-stage ovarian cancer patients who have
become refractory to standard chemotherapies. About Phenoxodiol
Phenoxodiol is an investigational drug and, as such, is not
marketed in the United States. Phenoxodiol is developed by
pharmaceutical company Marshall Edwards, Inc. which manages its
international research and development programs using the expertise
and clinical research capabilities of universities and hospitals in
the U.S., Australia and Europe. Marshall Edwards, Inc., has
licensed rights to bring phenoxodiol to market globally from its
parent company, Novogen Limited.
(ASX:NovogenASX:-ASX:Nasdaq:ASX:NVGN). Novogen is developing a
range of therapeutics across the fields of oncology, cardiovascular
disease and inflammatory diseases based on its phenolic drug
technology platform. More information on phenoxodiol and on the
Novogen group of companies can be found at
http://www.marshalledwardsinc.com/ and http://www.novogen.com/ .
Under U.S. law, a new drug cannot be marketed until it has been
investigated in clinical trials and approved by the FDA as being
safe and effective for the intended use. Statements included in
this press release that are not historical in nature are
"forward-looking statements" within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act
of 1995. You should be aware that our actual results could differ
materially from those contained in the forward-looking statements,
which are based on management's current expectations and are
subject to a number of risks and uncertainties, including, but not
limited to, our failure to successfully commercialize our product
candidates; costs and delays in the development and/or FDA
approval, or the failure to obtain such approval, of our product
candidates; uncertainties in clinical trial results; our inability
to maintain or enter into, and the risks resulting from our
dependence upon, collaboration or contractual arrangements
necessary for the development, manufacture, commercialization,
marketing, sales and distribution of any products; competitive
factors; our inability to protect our patents or proprietary rights
and obtain necessary rights to third arty patents and intellectual
property to operate our business; our inability to operate our
business without infringing the patents and proprietary rights of
others; general economic conditions; the failure of any products to
gain market acceptance; our inability to obtain any additional
required financing; technological changes; government regulation;
changes in industry practice; and one-time events. We do not intend
to update any of these factors or to publicly announce the results
of any revisions to these forward-looking statements. DATASOURCE:
Marshall Edwards, Inc. CONTACT: USA: David Sheon, +1-202-518-6384,
for Marshall Edwards, Inc.; Australia: Dr. Graham Kelly, Chairman
of Marshall Edwards, Inc., +61-2-9878-0088 Web site:
http://www.marshalledwardsinc.com/ http://www.novogen.com/
http://www.phenoxodiol.com/
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