Bladder NeoplasmsPhase 1/2NCT00393809
Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer
A Phase 1/2 study testing DTA-H19 in people with Bladder Neoplasms, run by Hebrew University of Jerusalem at 2 sites in Israel.
Trial summary
This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer who have failed intravesical therapy with Bacille Calmette-Guérin (BCG).DTA-H19 is a DNA plasmid that contains H19… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Neoplasms
- What is being tested?
- DTA-H19
- How many people
- 18 participants
- Where
- 2 sitesIsrael
- Study dates
- Jan 2006to Dec 2007
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have superficial transitional cell carcinoma of the bladder (stages Ta and/or CIS)
- Tumor biopsies must be shown to be positive for H19 gene by in situ hybridization
- Patients must have failed intravesical treatment with BCG
Who cannot join
- Patients with grade 3, or Stage 1 or higher stage TCC of the bladder
- Patients with any other malignancy that might impact 5-year survival or might be potentially confused with TCC
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Phase 1/2a, Dose-Escalation, Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer
This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer who have failed intravesical therapy with Bacille Calmette-Guérin (BCG).DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin [diphtheria toxin A (DTA) chain]only in cancer cells and not in normal cells. In line with the standard procedure for DNA plasmid pharmaceutical products, another chemical component will be added to the solution, called PEI (polyethlenimine) in a liquid solution, which improves the ability of the DNA plasmid to enter the cells.
Read the detailed description
This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer [stages Ta and carcinoma in situ (CIS)] who have failed intravesical therapy with Bacille Calmette-Guérin (BCG). The primary safety outcome measure is the maximum tolerated dose (MTD). DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin [diphtheria toxin A (DTA) chain]. This is a Patient-Oriented, Targeted Therapy as DTA expression is triggered by the presence of H19 transcription factors found only in bladder tumor and not normal bladder cells.
A maximum of 18 patients with histologically confirmed H19 positive superficial bladder cancer with multiple or recurrent stage Ta tumors or CIS will be included in this study. Patients with any grade 3, or any stage T1 or higher stage, will be excluded. This is a multicenter, dose escalation study in which, after eligibility criteria have been met, patients in five groups of 3 patients each, will receive escalating doses of DTA-H19 intravesically over a seven-week period. Treatments will be given weekly for three weeks followed one week later by safety and disease assessments, then another 3 weekly instillations will be performed. Each dose cohort will receive the same dose for all treatments. The first dose cohort will receive 2 mg of DTA-H19 plasmid per intravesical treatment for all treatments. The next dose cohort of 3 patients will receive 4 mg, the next 6 mg, the next 12 mg,and then the final dose cohort will receive 20 mg of DTA-H19 plasmid DNA. All doses will be mixed with polyethylenimine (PEI) to improve transduction efficiency. Doses will be escalated if none of the first three patients in the preceding dose cohort experience a dose limiting toxicity (DLT) after the first three weekly intravesical treatments.
Clinical responses will be assessed 4, 8, and 12 weeks after the start of treatment. If the stage Ta marker lesion is still present at the week 12 assessment, it will be resected by transurethral resection (TUR). Patients whose disease has not progressed (i.e., no new lesions, increase in the size of the marker lesion, by at least 50%, or increase in stage or any grade 3) will be offered continued once monthly treatments and follow-up for up to one year
- Conditions
- Bladder Neoplasms
- Being tested
- DTA-H19
- Keywords
- transitional cell carcinoma, H19 gene, plasmid, diphtheria toxin
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTA-H19Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
The maximum tolerated dose (MTD)
Secondary outcomes (3)
The percentage increase or reduction in the area of marker lesions
The number of patients with progressive disease
The time to disease progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2006 (estimated)
- Study startJan 2006
- Primary completionNov 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder NeoplasmsStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hebrew University of Jerusalem
- Sponsor type
- University, hospital or other
- Collaborators
- Anchiano Therapeutics Israel Ltd.
- Investigators
- Abraham Sidi, MD, Principal investigator, E. Wolfson Medical CenterIlan Leibovitch, MD, Principal investigator, Meir Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00393809
- Sponsor's protocol ID
- BC-05-02.CTIL
- Status last verified
- Dec 2007
- First submitted
- 26 Oct 2006
- Last updated
- 7 Jan 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2a, Dose-Escalation, Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer
- ClinicalTrials.gov ID
- NCT00393809
- Acronym / sponsor ID
- BC-05-02.CTIL
- Conditions
- Bladder Neoplasms
- Keywords
- transitional cell carcinoma, H19 gene, plasmid, diphtheria toxin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Hebrew University of JerusalemUniversity, hospital or other
- Collaborators
- Anchiano Therapeutics Israel Ltd.
- Study start
- Jan 2006
- Primary completion
- Nov 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 30 Oct 2006 (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 study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer who have failed intravesical therapy with Bacille Calmette-Guérin (BCG).DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin [diphtheria toxin A (DTA) chain]only in cancer cells and not in normal cells. In line with the standard procedure for DNA plasmid pharmaceutical products, another chemical component will be added to the solution, called PEI (polyethlenimine) in a liquid solution, which improves the ability of the DNA plasmid to enter the cells.
Detailed description
This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer [stages Ta and carcinoma in situ (CIS)] who have failed intravesical therapy with Bacille Calmette-Guérin (BCG). The primary safety outcome measure is the maximum tolerated dose (MTD). DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin [diphtheria toxin A (DTA) chain]. This is a Patient-Oriented, Targeted Therapy as DTA expression is triggered by the presence of H19 transcription factors found only in bladder tumor and not normal bladder cells.
A maximum of 18 patients with histologically confirmed H19 positive superficial bladder cancer with multiple or recurrent stage Ta tumors or CIS will be included in this study. Patients with any grade 3, or any stage T1 or higher stage, will be excluded. This is a multicenter, dose escalation study in which, after eligibility criteria have been met, patients in five groups of 3 patients each, will receive escalating doses of DTA-H19 intravesically over a seven-week period. Treatments will be given weekly for three weeks followed one week later by safety and disease assessments, then another 3 weekly instillations will be performed. Each dose cohort will receive the same dose for all treatments. The first dose cohort will receive 2 mg of DTA-H19 plasmid per intravesical treatment for all treatments. The next dose cohort of 3 patients will receive 4 mg, the next 6 mg, the next 12 mg,and then the final dose cohort will receive 20 mg of DTA-H19 plasmid DNA. All doses will be mixed with polyethylenimine (PEI) to improve transduction efficiency. Doses will be escalated if none of the first three patients in the preceding dose cohort experience a dose limiting toxicity (DLT) after the first three weekly intravesical treatments.
Clinical responses will be assessed 4, 8, and 12 weeks after the start of treatment. If the stage Ta marker lesion is still present at the week 12 assessment, it will be resected by transurethral resection (TUR). Patients whose disease has not progressed (i.e., no new lesions, increase in the size of the marker lesion, by at least 50%, or increase in stage or any grade 3) will be offered continued once monthly treatments and follow-up for up to one year
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients must have superficial transitional cell carcinoma of the bladder (stages Ta and/or CIS)
- Tumor biopsies must be shown to be positive for H19 gene by in situ hybridization
- Patients must have failed intravesical treatment with BCG
Key exclusion criteria (2 listed)
- Patients with grade 3, or Stage 1 or higher stage TCC of the bladder
- Patients with any other malignancy that might impact 5-year survival or might be potentially confused with TCC
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 |
|---|---|---|
| DTA-H19 | Drug | – |
Primary outcome
The maximum tolerated dose (MTD)
3 secondary outcomes
The percentage increase or reduction in the area of marker lesions
The number of patients with progressive disease
The time to disease progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2008.
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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.
Abraham Sidi, MD principal investigator
E. Wolfson Medical Center
Ilan Leibovitch, MD principal investigator
Meir Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DTA-H19 in people with Bladder Neoplasms, run by Hebrew University of Jerusalem at 2 sites in Israel.
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 3 inclusion and 2 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: finished, as of the sponsor's last update on 7 Jan 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The maximum tolerated dose (MTD). 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 7 Jan 2008.