A Phase I Neoadjuvant Study of In-situ REIC/Dkk-3 Therapy Followed By Prostatectomy in Patients With High Risk Localized Prostate Cancer
This is a phase I neoadjuvant gene therapy followed by prostatectomy, open-label,
dose-escalation trial for prostate cancer patients with high risk of local recurrence after
radical prostatectomy. Patients entered into this trial will have Prostate Cancer of
Clinical stage T1c, T2 or T3 with a Gleason Score of between 7 (4+3) and 10 at the time of
Patients will receive three 1 mL injections (3 mL total volume) of Ad-REIC/Dkk-3 into the
prostate under transrectal ultrasound-guidance (TRUS) and, patients will undergo a radical
prostatectomy four weeks after the injection.
Patients will receive treatment at one of three dose levels in a sequential dose-escalating
Three patients will be treated at each dose level unless a dose-limiting toxicity (DLT) is
observed or MFD (defined as 1 x 10e12 vp/treatment) is achieved. Enrollment will proceed to
the next dose level if 0 of 3 patients experiences a DLT; if one of the first 3 patients
experiences a DLT, three additional patients will be enrolled until a second patient
experiences a DLT (which defines the toxic dose) or until six total patients have been
treated at that dose level, whichever comes first. If a second DLT is not experienced within
that cohort, dose escalation may continue.
Additional patients will be enrolled a minimum of 14 days after treatment of the first
patient in the cohort (sentinel patient).
If 2 DLTs are observed within a cohort, enrollment into the cohort will cease and the dose
level immediately preceding that dose will be determined to be the MTD. If 2 non-lethal DLTs
are observed in Cohort 1, a lower dose cohort (Cohort -1) may be initiated.
Once the MTD is defined, an additional 3-6 patients may be enrolled at that dose level to
further evaluate safety of the MTD.
Patients will undergo a scheduled radical prostatectomy approximately 4 weeks after the
Ad-REIC/Dkk-3 injection. The prostate tissue removed will be retained and for those
patients treated at the MTD, assessed for REIC expression and evidence of apoptosis by TUNEL
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose
To define the Maximum Tolerated Dose (MTD) for intertumoral injection (IT) of Ad-REIC/Dkk-3 viral vector.
Simon Hall, MD
Mount Sinai School of Medicine
United States: Food and Drug Administration
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