Superficial Bladder CancerPhase 2NCT00595088
Phase 2b, Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer
A Phase 2 study testing BC-819/PEI in people with Superficial Bladder Cancer, run by Anchiano Therapeutics Israel Ltd. at 6 sites in 2 countries.
Trial summary
This study is designed to assess the efficacy and safety of DTA-H19/PEI given as six intravesical instillations of 20 mg of plasmid DNA complexed with PEI into the bladder of patients with intermediate risk superficial bladder cancer [recurrent stages Ta (low or high grade)and T1, (low grade) transitional cell… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Superficial Bladder Cancer
- What is being tested?
- BC-819/PEI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Jan 2008to Jan 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- To be eligible to participate in this study, patients must:
- Provide written informed consent.
- Have intermediate-risk recurrent superficial TCC of the bladder defined as Stage Ta (low or high grade) or T1 (but with penetration into no more than ½ of the lamina propria), low grade (grade 1 or grade 2), as confirmed by histopathology, and have not recurred within 3-months of a complete course of a prior acceptable therapy (i.e., 6-weekly intravesical administrations of BCG or standard adjuvant treatment with thiotepa, doxorubicin, epirubicin, valrubicin, or mitomycin C).
- Have complete resection of all papillary tumors with the exception of a single superficial papillary tumor that is appropriate to be a marker tumor (<1 cm in diameter).
- Have ≥ 2 tumor and ≤ 7 tumors visible during cystoscopy and no tumor larger than 3 cm in diameter. If only one tumor is present, it must be large enough to obtain a biopsy specimen adequate to determine the tumor stage and grade and leave a marker tumor.
- Have at least one tumor specimen resected before the start of the study that was positive for H19 expression by ISH. H19 expression positive is defined as >= 60 % of the tumor cells in the specimen expressing H19 at a moderate staining intensity.
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- Have failed at least one prior standard intravesical treatment including chemotherapy with mitomycin C, thiotepa, valrubicin, doxyrubicin, or epirubicin, or immunotherapy with BCG. Failure after treatment with chemotherapy is defined as recurrent disease after at least one intravesical instillation of drug. Failure after treatment with BCG is defined as intolerance to treatment such that treatment was discontinued or after having received 6 or more BCG instillations there is recurrent or persistent disease 3 or more months after initiation of BCG treatment.
- Have a Karnofsky's performance status of greater than or equal to 60%.
- Have adequate bone marrow reserve: Hemoglobin > 10 g/dL, WBC greater than or equal to 3000/mm3, and platelets > 100,000 /mm3.
- Have adequate renal function with serum creatinine < 1.5 x the laboratory upper limit of normal (ULN).
- Have adequate liver function with serum biliru¬bin, AST/SGOT and ALT/SGPT < 2 times the laboratory ULN.
- Be at least 18 years of age.
- If male, agree to use a condom, if sexually active, and if female, agree to practice one of the acceptable methods of birth control or be surgically sterile or postmenopausal (greater than 1 year post last menstrual cycle.
Who cannot join
- To be eligible to participate in this study, patients must not:
- Have current diagnosis or history of Stage T1 (high grade) or Stage T2 or higher or CIS.
- Have severe concomitant disease that might limit compliance or completion of the protocol.
- Have a tumor in a diverticulum, in the prostatic urethra, or covering the ureteral orifice.
- Have any other malignancy that might impact 5-year survival or might be potentially confused with TCC.
- Have congenital or acquired immune deficiencies.
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- Be receiving cytotoxic drugs or corticosteroids.
- Have received intravesical therapy within 8 weeks prior to study entry.
- Have received radiation therapy for their bladder cancer at any time or any other conditions including pelvic irradiation for any condition within 4 months prior to study entry.
- Have active infections (including urinary tract infections) defined as viral, bacterial, or fungal infections requiring therapy, HIV-positive status, concurrent febrile illness, or gross hematuria.
- Have biopsy, TUR, or traumatic catheterization within 14 days of start of treatment.
- If female, be pregnant or breast feeding.
- Have participated in any therapeutic research study within the last 8 weeks.
- Have participated in any other gene therapy study including patients who have received DTA-H19/PEI in the past.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Israel5 sites
Bnai Zion Medical Center
Haifa
Edith Wolfson Medical Center
Holon
Hadassah and Hebrew University Medical Center
Jerusalem
Meir Medical Center
Kfar Saba
Assaf Harofeh
Zrifin
About this study
Official title: Phase 2b, Multicenter Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer
This study is designed to assess the efficacy and safety of DTA-H19/PEI given as six intravesical instillations of 20 mg of plasmid DNA complexed with PEI into the bladder of patients with intermediate risk superficial bladder cancer [recurrent stages Ta (low or high grade)and T1, (low grade) transitional cell carcinoma (TCC)] who have failed prior intravesical therapies including either Bacillus Calmette-Guérin (BCG) or chemotherapy. The primary efficacy objective is to determine the effect of DTA-H19/PEI on the prevention of new tumors after the induction course of 6 weekly intravesical administrations of investigational product assessed 8 to 10 weeks after the start of treatment. Secondary objectives include assessing the ablative effect of DTA-H19/PEI on a marker tumor, safety assessed by the incidence and severity of adverse events, determining the long-term (46 weeks) continued rates of absence of bladder cancer, and time to tumor recurrence in those patients who had a complete response (CR) after the induction course.
Read the detailed description
DTA-H19, is a doubled stranded DNA plasmid that carries the gene for the diphtheria toxin A (DT-A) chain under the regulation of the H19 promoter sequence. This is a Patient-Oriented, Targeted Therapy as DT-A chain expression is triggered by the presence of H19 transcription factors that are upregulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment.
- Conditions
- Superficial Bladder Cancer
- Being tested
- BC-819/PEI
- Keywords
- Bladder Cancer, Refractory, inodiftagene vixteplasmid
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BC-819/PEIBiological
Also called DTA-H19
Papillary tumors will be resected with the exception of one marker tumor that will remain to examine the effects of the treatment on the remaining tumor. Study treatments will consist of an induction course of six weekly instillations of 20 mg of DTA-H19/PEI into the urinary bladder. Intravesical therapy will be delivered through a Foley catheter. Patients will be instructed to hold the dose in the bladder for two hours after administration. If the patient has a complete response, then she/he will be eligible to receive three additional courses of 3 weekly intravesical administrations of the same dose of investigational product every 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 20 mg of BC-819/PEI | Experimental | Six intravesical instillations of 20 mg of plasmid DNA (BC-819) complexed with PEI into the bladder of patients with intermediate-risk superficial bladder cancer [recurrent stages Ta (low or high grade) and T1 (low grade) TCC] who have failed prior intravesical therapies including BCG and/or chemotherapy. Receives: Biological: BC-819/PEI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Tumor Response Defined as the Absence of New Tumors
Tumor response evaluated at week 9 (range 8-10 weeks) during the first post induction course treatment cystoscopy or TUR of suspiciaous lesions
Measured: 9 Weeks
Secondary outcomes (2)
Time to Tumor Recurrence
The Time to Tumor Recurrence is defined as the interval between the date of the final tumor resection before the start of study treatments to the date when the cystoscopy was performed in which it was confirmed by histopathology that any suspicious lesions that were observed, were TCC of the bladder with the exception of the continued presence of the marker tumor at Week 9
Measured: 46 Weeks
Ablative Effect on a Marker Tumor
Complete disappearance of marker lesion
Measured: 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2008 (estimated)
- Study startJan 2008
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Superficial Bladder 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anchiano Therapeutics Israel Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Donald Lamm, MD, Principal investigator, University of Arizona and BCG Oncolgy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00595088
- Sponsor's protocol ID
- BC-07-01.CTIL
- Status last verified
- Apr 2019
- First submitted
- 7 Jan 2008
- Last updated
- 30 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2b, Multicenter Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer
- ClinicalTrials.gov ID
- NCT00595088
- Acronym / sponsor ID
- BC-07-01.CTIL
- Conditions
- Superficial Bladder Cancer
- Keywords
- Bladder Cancer, Refractory, inodiftagene vixteplasmid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Anchiano Therapeutics Israel Ltd.Industry (pharma, biotech, devices)
- Study start
- Jan 2008
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 16 Jan 2008 (estimated)
- Results
- Posted 21 Aug 2013
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 efficacy and safety of DTA-H19/PEI given as six intravesical instillations of 20 mg of plasmid DNA complexed with PEI into the bladder of patients with intermediate risk superficial bladder cancer [recurrent stages Ta (low or high grade)and T1, (low grade) transitional cell carcinoma (TCC)] who have failed prior intravesical therapies including either Bacillus Calmette-Guérin (BCG) or chemotherapy. The primary efficacy objective is to determine the effect of DTA-H19/PEI on the prevention of new tumors after the induction course of 6 weekly intravesical administrations of investigational product assessed 8 to 10 weeks after the start of treatment. Secondary objectives include assessing the ablative effect of DTA-H19/PEI on a marker tumor, safety assessed by the incidence and severity of adverse events, determining the long-term (46 weeks) continued rates of absence of bladder cancer, and time to tumor recurrence in those patients who had a complete response (CR) after the induction course.
Detailed description
DTA-H19, is a doubled stranded DNA plasmid that carries the gene for the diphtheria toxin A (DT-A) chain under the regulation of the H19 promoter sequence. This is a Patient-Oriented, Targeted Therapy as DT-A chain expression is triggered by the presence of H19 transcription factors that are upregulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 20 mg of BC-819/PEI | Experimental | Biological: BC-819/PEISix intravesical instillations of 20 mg of plasmid DNA (BC-819) complexed with PEI into the bladder of patients with intermediate-risk superficial bladder cancer [recurrent stages Ta (low or high grade) and T1 (low grade) TCC] who have failed prior intravesical therapies including BCG and/or chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Provide written informed consent.
- Have intermediate-risk recurrent superficial TCC of the bladder defined as Stage Ta (low or high grade) or T1 (but with penetration into no more than ½ of the lamina propria), low grade (grade 1 or grade 2), as confirmed by histopathology, and have not recurred within 3-months of a complete course of a prior acceptable therapy (i.e., 6-weekly intravesical administrations of BCG or standard adjuvant treatment with thiotepa, doxorubicin, epirubicin, valrubicin, or mitomycin C).
- Have complete resection of all papillary tumors with the exception of a single superficial papillary tumor that is appropriate to be a marker tumor (<1 cm in diameter).
- Have ≥ 2 tumor and ≤ 7 tumors visible during cystoscopy and no tumor larger than 3 cm in diameter. If only one tumor is present, it must be large enough to obtain a biopsy specimen adequate to determine the tumor stage and grade and leave a marker tumor.
- Have at least one tumor specimen resected before the start of the study that was positive for H19 expression by ISH. H19 expression positive is defined as >= 60 % of the tumor cells in the specimen expressing H19 at a moderate staining intensity.
Key exclusion criteria (14 listed)
- Have current diagnosis or history of Stage T1 (high grade) or Stage T2 or higher or CIS.
- Have severe concomitant disease that might limit compliance or completion of the protocol.
- Have a tumor in a diverticulum, in the prostatic urethra, or covering the ureteral orifice.
- Have any other malignancy that might impact 5-year survival or might be potentially confused with TCC.
- Have congenital or acquired immune deficiencies.
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 |
|---|---|---|
| BC-819/PEIAlso: DTA-H19Papillary tumors will be resected with the exception of one marker tumor that will remain to examine the effects of the treatment on the remaining tumor. Study treatments will consist of an induction course of six weekly instillations of 20 mg of DTA-H19/PEI into the urinary bladder. Intravesical therapy will be delivered through a Foley catheter. Patients will be instructed to hold the dose in the bladder for two hours after administration. If the patient has a complete response, then she/he will be eligible to receive three additional courses of 3 weekly intravesical administrations of the same dose of investigational product every 12 weeks. | Biological | 20 mg of BC-819/PEI |
Primary outcome
Complete Tumor Response Defined as the Absence of New Tumors
Time frame: 9 Weeks
Tumor response evaluated at week 9 (range 8-10 weeks) during the first post induction course treatment cystoscopy or TUR of suspiciaous lesions
2 secondary outcomes
Time to Tumor Recurrence
Time frame: 46 Weeks
Ablative Effect on a Marker Tumor
Time frame: 9 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Donald Lamm, MD principal investigator
University of Arizona and BCG Oncolgy
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BC-819/PEI in people with Superficial Bladder Cancer, run by Anchiano Therapeutics Israel Ltd. at 6 sites in 2 countries.
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 13 inclusion and 14 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 30 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Israel, 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 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?
Yes. Results are posted in the registry (first posted 21 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Tumor Response Defined as the Absence of New Tumors (time frame: 9 Weeks). 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 30 Apr 2019.