Gene Therapy in Treating Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Placing the gene for interleukin-12 into breast cancer cells may help the body build an immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gene therapy in treating women with metastatic breast cancer.

Detailed Description
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OBJECTIVES: Determine the toxicity and maximum tolerated dose of intratumoral injection of adenovirus-mediated human interleukin-12 gene in women with metastatic breast cancer. Determine the tumor response in patients treated with this regimen. Determine the immune response in patients treated with this regimen. OUTLINE: Patients receive a single dose of adenovirus-mediated human interleukin-12 intratumorally via percutaneous needle placement under ultrasound guidance. Blood and tumor tissue samples are collected periodically for immunological laboratory studies. Samples are analyzed for serum cytokine levels by ELISA; qualitative analysis of immune biomarkers by IHC staining; and immune cell biomarker analysis by FACS. After completion of study therapy, patients are followed periodically.

Official Title
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Phase I Trial of Adenoviral Vector Delivery of the Human Interleukin-12 cDNA by Intratumoral Injection in Patents With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: adenovirus-mediated human interleukin-12


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic adenocarcinoma of the breast Malignant disease in the skin, chest wall, or other sites (lymph nodes or primary tumor in the breast) accessible to percutaneous needle placement and injection Solitary or multiple tumors Measurable disease in ≥ 2 dimensions by physical examination or CT/MRI scan Malignant tumors in the skin and chest wall must be ≥ 4 mm in diameter by physical examination Malignant tumors in other accessible sites must be ≥ 1 cm in diameter on physical examination Malignant disease in other organs (in addition to skin or chest wall metastases) allowed Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Karnofsky performance status 70-100% Life expectancy ≥ 16 weeks Granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 mg/dL PT normal Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 45 mL/min Serum total bilirubin ≤ 2.0 times upper limit of normal (ULN) Serum transaminases ≤ 2.5 times ULN Not pregnant or nursing Negative pregnancy test Weight ≥ 30 kg (for patients treated with the highest dose level of study drug) No active infection or concurrent serious medical illness No HIV positivity No other malignancy within the past 5 years except for the following: Inactive nonmelanoma skin cancer In situ carcinoma of the cervix Grade 1 papillary bladder cancer PRIOR CONCURRENT THERAPY: More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) No anticoagulant therapy with heparin or warfarin for ≥ 2 months after completion of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: adenovirus-mediated human interleukin-12<br>starting dose of ADV-hIL12 - 1 x 10 to the 10th power vp (virus particles) per patient, escalating in half-log increments up to 1 x 10 to the 13th power vp per patient, after which dose escalation will be at lower increments of 2 x 10 to the 13th power vp, to a maximum of 3.0 x 10 to the 13th power vp per patient. | Biological: adenovirus-mediated human interleukin-12<br>* The purified ADV-hIL12 is suspended in formulation buffer (10mM Tris, pH 7.5/ 1mM MgCl2/ 150mM NaCl/ 10% glycerol) and aliquoted into 1ml cryovials. The filled vials are stored at or below -60 degC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose | Serum antibodies (titer) to adenovirus | up to 1 month | 
| Toxicity and safety | adverse events as assessed by NCI CTCAE v3.0 | up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response progression) | Sequential assessment of tumor on CT or MRI (complete response, partial response, stable disease, or disease) | up to 2 months | 
| Immune response | Serum IL12, and IFNγ levels. Serum antibodies (titer) to adenovirus. | up to 2 months | 

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