Gene Therapy Plus Chemotherapy in Treating Patients With Breast Cancer

February 6, 2013 updated by: National Cancer Institute (NCI)

Pilot Study of p53 Intralesional Gene Therapy With Chemotherapy in Breast Cancer

Phase I trial to study the effectiveness of gene therapy plus chemotherapy in treating patients who have breast cancer. Inserting the p53 gene into a person's cancer cells may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy. Combining chemotherapy with gene therapy may kill more tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Determine the effect of adenovirus p53 (Ad-p53) on chemotherapy-induced apoptosis in lesions in patients with breast cancer.

II. Determine p53 protein expression following intralesional injections of Ad-p53 by immunohistochemistry and reverse transcriptase polymerase chain reaction in this patient population.

III. Determine the time course and magnitude of the development of a humoral antibody response to the adenoviral vector in this patient population.

IV. Determine the ability of transfected p53 to upregulate downstream signals important in G1 arrest by assaying for WAF1 mRNA and apoptosis in this patient population.

V. Determine the toxicities and side effects of intralesional injections of Ad-p53 given in combination with standard chemotherapy in patients with cutaneous and subcutaneous metastatic breast cancer amenable to injections and biopsies.

VI. Determine if there is an increase in apoptosis induced by Ad-53 compared to baseline in this patient population.

OUTLINE:

Patients undergo biopsy of one of their skin nodules prior to any treatment. Patients receive the Ad-p53 gene therapy in one nodule and injection of a second nodule with Dulbecco's phosphate buffered saline. The next day, patients begin chemotherapy, which may be given weekly and continues every 21-28 days for up to 6 courses. On day 3, patients return for biopsy of injected nodules. Biopsies are only performed during the first course. Patients may receive further injections of the Ad-p53 gene with subsequent courses of chemotherapy, for up to six courses.

Patients are followed monthly for 4 months.

Study Type

Interventional

Enrollment (Actual)

20

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
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase 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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed epithelial breast cancer
  • At least 3 cutaneous or subcutaneous lesions required
  • Measurable disease that includes, but is not limited to, cutaneous or subcutaneous metastases

PATIENT CHARACTERISTICS:

  • Age: Over 18
  • Performance status: ECOG 0-2
  • Absolute granulocyte count at least 1,500/mm3
  • Hemoglobin greater than 8 g/dL
  • Platelet count greater than 100,000/mm3
  • Bilirubin less than 2 mg/dL
  • PT/PTT within normal range
  • SGOT/SGPT less than 2 times upper limit of normal
  • Creatinine less than 1.8 mg/dL
  • Not pregnant
  • Fertile patients must use effective contraception during and for 3 months after therapy

PRIOR CONCURRENT THERAPY:

  • Concurrent cytotoxic chemotherapy allowed, if stable and responding
  • At least 4 weeks since prior chemotherapy, if starting a new regimen
  • At least 4 weeks since radiotherapy
  • Prior adjuvant radiotherapy to the chest wall allowed
  • At least 6 months since radiotherapy to lesions that are to be injected
  • Recovered from prior therapy

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: Arm I
Patients undergo biopsy of one of their skin nodules prior to any treatment. Patients receive the Ad-p53 gene therapy in one nodule and injection of a second nodule with Dulbecco's phosphate buffered saline. The next day, patients begin chemotherapy, which may be given weekly and continues every 21-28 days for up to 6 courses. On day 3, patients return for biopsy of injected nodules. Biopsies are only performed during the first course. Patients may receive further injections of the Ad-p53 gene with subsequent courses of chemotherapy, for up to six courses.
Drug: chemotherapy
Biological: Ad5CMV-p53 gene

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Margaret von Mehren, MD, Fox Chase 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

January 1, 1999

Primary Completion (Actual)

May 1, 2001

Study Registration Dates

First Submitted

December 10, 1999

First Submitted That Met QC Criteria

May 19, 2004

First Posted (Estimate)

May 20, 2004

Study Record Updates

Last Update Posted (Estimate)

February 7, 2013

Last Update Submitted That Met QC Criteria

February 6, 2013

Last Verified

June 1, 2001

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02273
  • FCCC-97009
  • NCI-T97-0042
  • CDR0000066480 (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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