Gene Therapy Plus Chemotherapy in Treating Patients With Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004038
First received: December 10, 1999
Last updated: February 6, 2013
Last verified: June 2001
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Biological: Ad5CMV-p53 gene
Drug: chemotherapy
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of p53 Intralesional Gene Therapy With Chemotherapy in Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 20
Study Start Date: January 1999
Primary Completion Date: May 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: Ad5CMV-p53 gene Drug: chemotherapy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004038

Locations
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Investigators
Study Chair: Margaret von Mehren, MD Fox Chase Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004038     History of Changes
Other Study ID Numbers: NCI-2012-02273, FCCC-97009, NCI-T97-0042, CDR0000066480
Study First Received: December 10, 1999
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage I breast cancer
stage II breast cancer
stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 20, 2014