Gene Therapy Plus Chemotherapy in Treating Patients With Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: Ad5CMV-p53 gene
* Drug: chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br> <br> Drug: chemotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I breast cancer, stage II breast cancer, stage IV breast cancer, stage IIIA breast cancer, recurrent breast cancer, stage IIIB breast cancer