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A Phase I Neoadjuvant Study of In-situ REIC/Dkk-3 Therapy Followed By Prostatectomy in Patients With High Risk Localized Prostate Cancer

Phase 1
20 Years
75 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

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

Inclusion Criteria:

1. Male aged between 20 and 75 years (inclusive) with histologically documented
clinically localized, adenocarcinoma of the prostate scheduled to undergo a radical

2. Patient with clinical stage T1c, T2 or T3 with Primary Gleason score of 4 [total
Gleason score of between 7 (4+3) and 10] at time of assessment for this trial.

3. Recent (≤ 3 months prior to study entry) negative bone scan and CT scan of

4. Life expectancy of at least 10 years.

5. In good general health, free from clinically significant illness or disease (as
determined by medical/surgical history, physical examination, weight, 12-lead ECG,
and clinical laboratory tests)

6. Appropriate surgical candidate for radical prostatectomy and a performance status of
≤ 2 (Zubrod scale)

7. Patients should have adequate bone marrow function defined as an absolute peripheral
granulocyte count ≥ 1,500 and platelet count of ≥ 100,000, adequate hepatic function
with a total bilirubin ≤ 1.5 mg/dl and ALT < 4x the upper limits of normal, adequate
renal function defined as serum creatinine ≤ 2.0 mg/dl

8. Body Mass Index ≥ 18 and ≤ 35 kg/m2

9. Patients must have normal coagulation profile (PT, PTT) and no history of substantial
non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only
(for control of central line patency).

10. Patient is willing to refrain from sexual activity or agrees to use a barrier
contraceptive device (e.g. condom) after treatment with Ad-REIC/Dkk-3 and until the
prostatectomy operation.

11. Patients must sign an informed consent indicating that they are aware of the
investigational nature of the study, in keeping with the policies of the institution.

Exclusion Criteria:

1. Previous or current hormonal treatment, chemotherapy, radiation therapy,
immunotherapy or other investigational status drug within the past 4 weeks.

2. Unable to tolerate transrectal ultrasound.

3. Patients who are not appropriate surgical candidates for radical prostatectomy based
on the evaluation of co-existent medical diseases and competing causes of death.

4. Patients with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric
disorders are not eligible.

5. Patients who are HIV positive or have chronic hepatitis B or C infections are not
eligible (because of possible immune effects of these conditions).

6. Patients with a clinical history of primary or secondary immunodeficiency, autoimmune
disease or patients taking immunosuppressive drugs such as corticosteroids
continuously for > 4 months [> 5 mg hydrocortisone/day] are ineligible. (The
experimental treatment being evaluated in this protocol depends on an intact immune
system. Patients who have a decreased immune competence may be less responsive to the
experimental treatment and more susceptible to its toxicities.)

7. As a result of medical review, physical examination, the Principal Investigator (or
medically qualified nominee) considers the subject unfit for the study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Description:

To define the Maximum Tolerated Dose (MTD) for intertumoral injection (IT) of Ad-REIC/Dkk-3 viral vector.

Outcome Time Frame:


Safety Issue:


Principal Investigator

Simon Hall, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mount Sinai School of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

September 2010

Completion Date:

November 2012

Related Keywords:

  • Prostate Cancer
  • Prostate Cancer
  • Prostatectomy
  • Postectomy
  • Oncology
  • REIC
  • Dikkoff
  • Apoptosis
  • Prostatic Neoplasms



Mount Sinai School of MedicineNew York, New York  10029