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

Study start date: May 1, 1998

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 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 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