Neoadjuvant Study of In-situ REIC/Dkk-3 in Prostate Cancer

NCT01197209 | Withdrawn Phase 1 DMC

• 1 other identifier: MTG-REIC-PC001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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 enrollment. Patients will receive three 1 mL injections (3 mL total volume) of Ad-REIC/Dkk-3 into the prostate prior to undergoing a radical prostatectomy. 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 with expansion for up to 6 more patients at the MTD or MFD.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Prostatectomy; Postectomy; Oncology; REIC; Dikkoff; Apoptosis

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

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

  7-days

• Safety evaluation of adverse drug experiences compared with historical precedence

  To assess the safety of in-situ therapy with REIC/Dkk-3 gene in prostate cancer patients with high risk of local recurrence after radical prostatectomy. Safety events will be evaluated and assessed with regards to causality and in comparison with historical precedence for this patient population.

  28-days

Secondary Outcomes (1)

• Pharmacodynamic Efficacy Markers

  28-days

Study Arms (1)

Ad-REIC/Dkk-3 Arm

EXPERIMENTAL

Active arm on Ad-REIC/Dkk-3

Biological: Ad-REIC/Dkk-3

Interventions

Ad-REIC/Dkk-3 BIOLOGICAL

REIC (Reduced Expression in Immortalized Cells) protein is down regulated in a variety of cancer cell lines including prostate tumors. The REIC gene is identical to the Dickkopf-3 (Dkk-3) gene that is a member of the Dickkopf gene family. Ad-REIC/Dkk-3 is designed as a viral vector that delivers a DNA plasmid capable of producing intracellular REIC protein. The expression plasmid includes the full-length human cDNA sequence for REIC. The adenovirus vector is a transport mechanism to infuse the REIC/Dkk-3 plasmid into the cell providing a temporary transfusion of REIC protein.

Ad-REIC/Dkk-3 Arm

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male aged between 20 and 75 years (inclusive) with histologically documented clinically localized, adenocarcinoma of the prostate scheduled to undergo a radical prostatectomy.
• 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.
• Recent (≤ 3 months prior to study entry) negative bone scan and CT scan of abdomen/pelvis.
• Life expectancy of at least 10 years.
• 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)
• Appropriate surgical candidate for radical prostatectomy and a performance status of ≤ 2 (Zubrod scale)
• 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
• Body Mass Index ≥ 18 and ≤ 35 kg/m2
• 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).
• 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.
• 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.

You may not qualify if:

• Previous or current hormonal treatment, chemotherapy, radiation therapy, immunotherapy or other investigational status drug within the past 4 weeks.
• Unable to tolerate transrectal ultrasound.
• Patients who are not appropriate surgical candidates for radical prostatectomy based on the evaluation of co-existent medical diseases and competing causes of death.
• Patients with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorders are not eligible.
• Patients who are HIV positive or have chronic hepatitis B or C infections are not eligible (because of possible immune effects of these conditions).
• 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.)
• As a result of medical review, physical examination, the Principal Investigator (or medically qualified nominee) considers the subject unfit for the study.

Sponsors & Collaborators

• Momotaro-Gene Inc.: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Links

• Momotaro-Gene Website

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Simon Hall, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 9, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: August 23, 2013

Record last verified: 2013-08

Locations

US (1)