OUR SCIENCE
Prolanta™
The first clinical trial of Prolanta to treat
ovarian and breast cancer
is anticipated to begin in Q2 2011. The
preclinical testing required prior to the first-in-human clinical
trial will
be complete by Q4 2010. The Phase I trial will be an open-label
safety
and pharmacokinetic study in women aged 18 to 70 (non-pregnant, women of
childbearing age either on birth control or who have undergone an oophorectomy)
with advanced metastatic breast and ovarian cancer. The trial will test four
escalating doses in cohorts of three to six patients over 14 days of daily
subcutaneous administration. The primary
objective of this study will be to
evaluate the tolerability and determine the optimal dose of Prolanta.
The
safety evaluation will be determined by assessing adverse events, physical
examination, electrocardiogram, changes in clinical laboratory results including
clinical chemistry, hematology and urinalysis and vital signs including blood
pressure, pulse and respiratory rate. The optimal dose of Prolanta will be
determined by evaluating both the safety profile and blood levels of Prolanta.
Two Phase IIA trials are planned; one in metastatic ovarian cancer and one in
metastatic breast cancer. These trials
will be open label, randomized, controlled trials evaluating the optimal dose of
Prolanta added to standard of care chemotherapy, in patients who have relapsed
after first (ovarian cancer patients) or second or third line chemotherapy
(breast cancer patients). Approximately
30 patients will be enrolled in each trial, with a 2:1
randomization of Prolanta plus chemotherapy to chemotherapy only. Patients in
the treatment groups will receive up to three months of daily subcutaneous
injections of Prolanta at the optimal dose, along with chemotherapy.
The primary objective of these trials
will be to determine the effect of Prolanta on progression-free survival.
Tumor response will be determined by RECIST (Response Evaluation
Criteria in Solid Tumors)
criteria.
Safety and the pharmacokinetics of
Prolanta in combination with the chemotherapy will also be studied.
Various tumor proteins will be analyzed from tumor biopsies obtained before and
after the treatment period to evaluate the pharmacodynamics of Prolanta and to
identify a potential biomarker to identify patients that may respond to
treatment with Prolanta for future trials.
Tumor markers to be analyzed may include Ki67 and PCNA (both markers of
cell proliferation), PRL, PRLR, Bcl-2, and phosphorylated MAPK, STAT3 and STAT5
proteins. The serum protein CA-125 will be evaluated in the ovarian cancer
patients.
The first Phase IIB trial is planned for the ovarian cancer indication. The
purpose of this study is to compare progression-free survival in patients with
advanced ovarian cancer treated with Prolanta in combination with carboplatin
and paclitaxel versus placebo in combination with carboplatin and paclitaxel.
This trial will be a double-blinded (subject, caregiver, investigator,
outcomes assessor), randomized, placebo-controlled trial evaluating Prolanta in
combination with chemotherapy in patients that have relapsed at least 6 months
following treatment cessation of first-line platinum-containing therapy.
A sample size will be determined that will have 80% power to detect the
difference at a 2-sided alpha level of 0.05 using a log-rank test for equality
of survival curves. The sample size is
anticipated to fall between 120 and 150 patients.
Treatment of the patients will continue until signs of disease
progression occur or side effects of the chemotherapy necessitate cessation. The
primary outcome measure will be progression-free survival. Secondary outcome
measures will include overall survival, safety and tolerability, and objective
tumor response, as evaluated by RECIST criteria.
Tumor markers will be analyzed from tumor biopsies obtained before and
after the treatment period, as described above.
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