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A Phase I Trial of Intravesical Ad-p53 Treatment in Locally Advanced and Metastatic Bladder Cancer

Phase 1
18 Years
Not Enrolling
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

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Trial Information

A Phase I Trial of Intravesical Ad-p53 Treatment in Locally Advanced and Metastatic Bladder Cancer


I. 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

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).

Inclusion Criteria:

- 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

- 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

- 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

Exclusion Criteria:

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose as assessed by NCI Common Terminology Criteria (CTC) version 2.0

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Lance Pagliaro

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 1998

Completion Date:

Related Keywords:

  • 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
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Transitional Cell



M D Anderson Cancer Center Houston, Texas  77030