Prostate CancerPhase 1NCT01197209
Neoadjuvant Study of In-situ REIC/Dkk-3 in Prostate Cancer
A Phase 1 study testing Ad-REIC/Dkk-3 in people with Prostate Cancer, run by Momotaro-Gene Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 75 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Ad-REIC/Dkk-3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Dec 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai School of Medicine
New York, New York, 10029
About this study
Official title: 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 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.
Read the detailed description
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 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 design.
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 staining.
- Conditions
- Prostate Cancer
- Being tested
- Ad-REIC/Dkk-3
- Keywords
- Prostate Cancer, Prostatectomy, Postectomy, Oncology, REIC, Dikkoff, Apoptosis
- Medical subject headings
- Prostatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad-REIC/Dkk-3Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| Ad-REIC/Dkk-3 Arm | Experimental | Active arm on Ad-REIC/Dkk-3 Receives: Biological: Ad-REIC/Dkk-3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
To define the Maximum Tolerated Dose (MTD) for intertumoral injection (IT) of Ad-REIC/Dkk-3 viral vector.
Measured: 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.
Measured: 28-days
Secondary outcomes (1)
Pharmacodynamic Efficacy Markers
To assess the effectiveness of Ad-REIC/Dkk-3 in the treatment of prostate cancer as evaluated by the PSA biomarker and histologic examination of extracted prostate tissue.
Measured: 28-days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: Suspended due to change in development plans and investigator
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Momotaro-Gene Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Icahn School of Medicine at Mount Sinai
- Responsible party
- Sponsor
- Investigators
- Simon Hall, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01197209
- Sponsor's protocol ID
- MTG-REIC-PC001
- Status last verified
- Aug 2013
- First submitted
- 3 Sep 2010
- Last updated
- 23 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Neoadjuvant Study of In-situ REIC/Dkk-3 Therapy Followed By Prostatectomy in Patients With High Risk Localized Prostate Cancer
- ClinicalTrials.gov ID
- NCT01197209
- Acronym / sponsor ID
- MTG-REIC-PC001
- Conditions
- Prostate Cancer
- Keywords
- Prostate Cancer, Prostatectomy, Postectomy, Oncology, REIC, Dikkoff, Apoptosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Suspended due to change in development plans and investigator
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Momotaro-Gene Inc.Industry (pharma, biotech, devices)
- Collaborators
- Icahn School of Medicine at Mount Sinai
- Study start
- Sep 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 9 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 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 design.
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 staining.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ad-REIC/Dkk-3 Arm | Experimental | Biological: Ad-REIC/Dkk-3Active arm on Ad-REIC/Dkk-3 |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ad-REIC/Dkk-3REIC (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. | Biological | Ad-REIC/Dkk-3 Arm |
Primary outcome
Maximum Tolerated Dose
Time frame: 7-days
To define the Maximum Tolerated Dose (MTD) for intertumoral injection (IT) of Ad-REIC/Dkk-3 viral vector.
Safety evaluation of adverse drug experiences compared with historical precedence
Time frame: 28-days
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.
1 secondary outcome
Pharmacodynamic Efficacy Markers
Time frame: 28-days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2013.
- Momotaro-Gene WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Simon Hall, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ad-REIC/Dkk-3 in people with Prostate Cancer, run by Momotaro-Gene Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: 7-days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2013.