Recurrent Bladder CancerPhase 1NCT00003167
Gene Therapy in Treating Patients With Advanced Bladder Cancer
A Phase 1 study testing Ad5CMV-p53 gene in people with Recurrent Bladder Cancer and Stage I Bladder Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase I trial to study the effectiveness of gene therapy in treating patients with advanced bladder cancer. Inserting the p53 gene into a person's bladder cancer cells may improve the body's ability to fight cancer Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Bladder Cancer, Stage I Bladder Cancer, Stage II Bladder Cancer
- What is being tested?
- Ad5CMV-p53 gene
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- May 1998to Dec 2002
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- TCC of the bladder which is muscle-invasive and has demonstrated resistance to platinum-based chemotherapy, or tumor stage T1 that has either failed BCG or has concomitant CIS
- Patients will be eligible if they are if they are inappropriate for cystectomy because of metastatic disease or are medically unfit for surgery, or if they have refused cystectomy
- Patients without muscle invasion (TI) must have concomitant carcinoma in situ (CIS) or have recurrent/persistent tumor following at least 1 course of intravesical bacillus Calmette-guerin (BCG) immunotherapy
- Patients who have receive BCG and have only CIS are also eligible if the lesions are sufficient raised and demarcated to be measurable (must be approved by Dr. Dinney)
- Patients must have negative adenoviral culture of urine prior to treatment; patients may be registered if the culture is negative after 14 days
- Local-regional disease will be defined as those patients who have evidence of locally unresectable disease by examination under anesthesia (pelvic sidewall fixation, invasion of central genitalia, or nodal involvement
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- Pelvic nodal involvement will be biopsy documented; patients in the nodal category will include those with either mediastinal, para-aortic, or supraclavicular involvement
- Distant visceral disease will include those patients with documented of distant visceral sites (lung, bone, liver); a biopsy will not be required in the patients with characteristic radiographic evidence of metastases
- Patients with muscle invasion must have failed to respond to CDDP-based chemotherapy or have recurrent/persistent tumor after chemotherapy; patients who are not candidates for CDDP-based chemotherapy because of poor cardiac function, renal function, or performance status are also eligible
- Expected survival > 12 weeks
- Bidimensionally measurable disease; vigorous transurethral resection should be avoided prior to study
- Zubrod performance status less than or equal to 2
- Patients have voluntarily signed an informed consent in accordance with institutional policies
- Negative pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized); females and males must agree to use barriers method of birth control while on study
- Negative serology for human immunodeficiency virus
Who cannot join
- Patients must have some control of bladder function; patients with NCI grade 3 incontinence are not eligible
- Patients who have had prior gene therapy, radiotherapy within 6 weeks, or chemotherapy within 21 days prior to study treatment (42 for mitomycin C and nitrosoureas); patients must have recovered from any toxicity of prior chemotherapies and may manifest at most grade 2 toxicity in any organ system from prior therapy
- Patient may not have any concurrent use of other investigational agents
- Pregnant or lactating females are excluded
- Patients who have active viral, bacterial, or fungal infections requiring treatment, or who have serious concurrent illness or psychological, familial, sociological, geographical, or other conditions which do not permit adequate follow-up and compliance with study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of Intravesical Ad-p53 Treatment in Locally Advanced and Metastatic Bladder Cancer
Phase I trial to study the effectiveness of gene therapy in treating patients with advanced bladder cancer. Inserting the p53 gene into a person's bladder cancer cells may improve the body's ability to fight cancer
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the safety and toxicity of adenovirus p53 (Ad-p53) gene therapy in patients with locally advanced or metastatic bladder cancer.
II. Measure infection with Ad-p53 and confirm expression of p53 after infection.
III. Characterize clinical response of measurable tumor in these patients. IV. Determine the duration of effect of this treatment in these patients. V. Define the time course of elimination of vector from urinary bladder.
OUTLINE: This is a dose escalation study.
Group 1 patients receive adenovirus p53 (Ad-p53) intravesically on days 1 and 4. Treatment continues every 4 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3 patients in group 1 receive escalating doses of Ad-p53. In the absence of grade 3 or worse toxicity in the first 3 patients treated, subsequent cohorts of 3 patients each receive escalating doses of Ad-p53 on the same schedule. If 1 of 3 patients experiences grade 3 toxicity, an additional 3 patients are treated at that dose level and dose escalation continues. If 1 of 3 patients experience grade 4 toxicity or 2 of 3 patients experience grade 3 toxicity, dose escalation ceases and the MTD is defined as the previous dose level. Group 2 patients receive Ad-p53 at the MTD on days 1-4, and group 3 patients receive Ad-p53 at the MTD on days 1-4 and 8-11.
Patients are followed on day 28, then every 3 months for 1 year or until disease progression.
PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for this study (3-12 patients for group 1; 3-6 patients for group 2; and 6 patients for group 3).
- Conditions
- Recurrent Bladder Cancer, Stage I Bladder Cancer, Stage II Bladder Cancer, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder
- Being tested
- Ad5CMV-p53 gene
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad5CMV-p53 geneBiological
Also called Ad5CMV-p53, ADVEXIN, INGN-201
Given intravesically
| Study group | Role | What they receive |
|---|---|---|
| Treatment (adenovirus p53) | Experimental | Group 1 patients receive adenovirus p53 (Ad-p53) intravesically on days 1 and 4. Treatment continues every 4 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3 patients in group 1 receive escalating doses of Ad-p53. In the absence of grade 3 or worse toxicity in the first 3 patients treated, subsequent cohorts of 3 patients each receive escalating doses of Ad-p53 on the same schedule. If 1 of 3 patients experiences grade 3 toxicity, an additional 3 patients are treated at that dose level and dose escalation continues. If 1 of 3 patients experience grade 4 toxicity or 2 of 3 patients experience grade 3 toxicity, dose escalation ceases and the MTD is defined as the previous dose level. Group 2 patients receive Ad-p53 at the MTD on days 1-4, and group 3 patients receive Ad-p53 at the MTD on days 1-4 and 8-11. Receives: Biological: Ad5CMV-p53 gene |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated dose as assessed by NCI Common Terminology Criteria (CTC) version 2.0
Measured: 4 weeks
Safety and toxicity of adenovirus p53 (Ad-p53) gene therapy according to NCI CTC version 2.0
Measured: Up to 1 year after completion of treatment
Secondary outcomes (1)
Clinical response
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2003 (estimated)
- Study startMay 1998
- Primary completionDec 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Bladder CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lance Pagliaro, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003167
- Sponsor's protocol ID
- NCI-2012-02261
- Other IDs
- MDA-DM-96172, R21CA076233, CDR0000065968
- Status last verified
- Jan 2013
- First submitted
- 1 Nov 1999
- Last updated
- 23 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Intravesical Ad-p53 Treatment in Locally Advanced and Metastatic Bladder Cancer
- ClinicalTrials.gov ID
- NCT00003167
- Acronym / sponsor ID
- NCI-2012-02261
- Conditions
- Recurrent Bladder Cancer, Stage I Bladder Cancer, Stage II Bladder Cancer, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 1998
- Primary completion
- Dec 2002 (actual)
- First posted
- 25 Nov 2003 (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.
Phase I trial to study the effectiveness of gene therapy in treating patients with advanced bladder cancer. Inserting the p53 gene into a person's bladder cancer cells may improve the body's ability to fight cancer
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety and toxicity of adenovirus p53 (Ad-p53) gene therapy in patients with locally advanced or metastatic bladder cancer.
II. Measure infection with Ad-p53 and confirm expression of p53 after infection.
III. Characterize clinical response of measurable tumor in these patients. IV. Determine the duration of effect of this treatment in these patients. V. Define the time course of elimination of vector from urinary bladder.
OUTLINE: This is a dose escalation study.
Group 1 patients receive adenovirus p53 (Ad-p53) intravesically on days 1 and 4. Treatment continues every 4 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3 patients in group 1 receive escalating doses of Ad-p53. In the absence of grade 3 or worse toxicity in the first 3 patients treated, subsequent cohorts of 3 patients each receive escalating doses of Ad-p53 on the same schedule. If 1 of 3 patients experiences grade 3 toxicity, an additional 3 patients are treated at that dose level and dose escalation continues. If 1 of 3 patients experience grade 4 toxicity or 2 of 3 patients experience grade 3 toxicity, dose escalation ceases and the MTD is defined as the previous dose level. Group 2 patients receive Ad-p53 at the MTD on days 1-4, and group 3 patients receive Ad-p53 at the MTD on days 1-4 and 8-11.
Patients are followed on day 28, then every 3 months for 1 year or until disease progression.
PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for this study (3-12 patients for group 1; 3-6 patients for group 2; and 6 patients for group 3).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (adenovirus p53) | Experimental | Biological: Ad5CMV-p53 geneGroup 1 patients receive adenovirus p53 (Ad-p53) intravesically on days 1 and 4. Treatment continues every 4 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3 patients in group 1 receive escalating doses of Ad-p53. In the absence of grade 3 or worse toxicity in the first 3 patients treated, subsequent cohorts of 3 patients each receive escalating doses of Ad-p53 on the same schedule. If 1 of 3 patients experiences grade 3 toxicity, an additional 3 patients are treated at that dose level and dose escalation continues. If 1 of 3 patients experience grade 4 toxicity or 2 of 3 patients experience grade 3 toxicity, dose escalation ceases and the MTD is defined as the previous dose level. Group 2 patients receive Ad-p53 at the MTD on days 1-4, and group 3 patients receive Ad-p53 at the MTD on days 1-4 and 8-11. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- TCC of the bladder which is muscle-invasive and has demonstrated resistance to platinum-based chemotherapy, or tumor stage T1 that has either failed BCG or has concomitant CIS
- Patients will be eligible if they are if they are inappropriate for cystectomy because of metastatic disease or are medically unfit for surgery, or if they have refused cystectomy
- Patients without muscle invasion (TI) must have concomitant carcinoma in situ (CIS) or have recurrent/persistent tumor following at least 1 course of intravesical bacillus Calmette-guerin (BCG) immunotherapy
- Patients who have receive BCG and have only CIS are also eligible if the lesions are sufficient raised and demarcated to be measurable (must be approved by Dr. Dinney)
- Patients must have negative adenoviral culture of urine prior to treatment; patients may be registered if the culture is negative after 14 days
Key exclusion criteria (5 listed)
- Patients must have some control of bladder function; patients with NCI grade 3 incontinence are not eligible
- Patients who have had prior gene therapy, radiotherapy within 6 weeks, or chemotherapy within 21 days prior to study treatment (42 for mitomycin C and nitrosoureas); patients must have recovered from any toxicity of prior chemotherapies and may manifest at most grade 2 toxicity in any organ system from prior therapy
- Patient may not have any concurrent use of other investigational agents
- Pregnant or lactating females are excluded
- Patients who have active viral, bacterial, or fungal infections requiring treatment, or who have serious concurrent illness or psychological, familial, sociological, geographical, or other conditions which do not permit adequate follow-up and compliance with study protocol
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 |
|---|---|---|
| Ad5CMV-p53 geneAlso: Ad5CMV-p53, ADVEXIN, INGN-201Given intravesically | Biological | Treatment (adenovirus p53) |
Primary outcome
Maximum-tolerated dose as assessed by NCI Common Terminology Criteria (CTC) version 2.0
Time frame: 4 weeks
Safety and toxicity of adenovirus p53 (Ad-p53) gene therapy according to NCI CTC version 2.0
Time frame: Up to 1 year after completion of treatment
1 secondary outcome
Clinical response
Time frame: Up to 1 year
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 23 Jan 2013.
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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.
Lance Pagliaro principal investigator
M.D. Anderson Cancer Center
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 Ad5CMV-p53 gene in people with Recurrent Bladder Cancer and Stage I Bladder Cancer, run by National Cancer Institute (NCI) 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 15 inclusion and 5 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 23 Jan 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 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?
Maximum-tolerated dose as assessed by NCI Common Terminology Criteria (CTC) version 2.0 (time frame: 4 weeks). 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 Jan 2013.