Gene Therapy in Treating Patients With Advanced Bladder Cancer

January 22, 2013 updated by: National Cancer Institute (NCI)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

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 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 Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (adenovirus p53)

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.
Biological: Ad5CMV-p53 gene
Given intravesically
Other Names:
  • Ad5CMV-p53
  • ADVEXIN
  • INGN-201

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum-tolerated dose as assessed by NCI Common Terminology Criteria (CTC) version 2.0
Time Frame: 4 weeks
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
Up to 1 year after completion of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Clinical response
Time Frame: Up to 1 year
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Lance Pagliaro, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 1998

Primary Completion (Actual)

December 1, 2002

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

November 24, 2003

First Posted (Estimate)

November 25, 2003

Study Record Updates

Last Update Posted (Estimate)

January 23, 2013

Last Update Submitted That Met QC Criteria

January 22, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02261
  • MDA-DM-96172
  • R21CA076233 (U.S. NIH Grant/Contract)
  • CDR0000065968 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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