Biological Therapy in Treating Women With Breast Cancer That Has Spread to the Liver

Study Overview
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Brief Summary
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RATIONALE: Biological therapy using a gene-modified virus that can make interleukin-12 may help the body build an effective immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of a gene-modified virus that can make interleukin-12 in treating women with breast cancer that has spread to the liver.

Detailed Description
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Direct intratumoral injection of metastatic hepatic tumors using an adenoviral vector expressing the human recombinant interleukin-12 gene (Adv.RSV-hIL12, also termed ADV-hIL-12). OBJECTIVES: Study the toxicity of escalating doses of adenoviral vector expressing the human recombinant interleukin-12 gene, administered by percutaneous intratumoral injection, in women with liver metastasis secondary to breast cancer. Determine tumor responses produced by this regimen. Determine immune responses induced by this regimen.

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

Conditions
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Breast Cancer, Metastatic 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* breast adenocarcinoma metastatic to the liver Solitary or multiple hepatic metastases No malignant involvement of > 40% of the estimated liver volume NOTE: *Must be from the hepatic tumor designated for study injection Metastatic liver tumors must be measurable in ≥ 2 dimensions on CT scan or MRI At least 1 metastatic hepatic tumor ≥ 2 cm in diameter must be visualized by ultrasound and accessible for percutaneous injection under ultrasound guidance Extrahepatic metastasis allowed No solitary hepatic metastasis eligible for liver resection No clinical evidence for severe liver disease (e.g., prior or current ascites or portosystemic encephalopathy) Hormone-receptor status not specified PATIENT CHARACTERISTICS: Female Menopausal status not specified Granulocyte count ≥ 1,500/mm^3 Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 100,000/mm^3 PT ≤ 14.5 sec Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 45 mL/min Bilirubin ≤ 2 times upper limit of normal (ULN) Transaminases ≤ 2.5 times ULN Karnofsky performance status ≥ 70% Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 2 months after completion of study treatment No active infection or serious intercurrent medical illness No HIV infection Life expectancy ≥ 16 weeks No other malignancy within the past 5 years except inactive nonmelanoma skin cancer, in situ carcinoma of the cervix, or grade 1 papillary bladder cancer At highest dose level, patient must weigh ≥ 30 kg PRIOR CONCURRENT THERAPY: No systemic immunosuppressive drugs, including corticosteroids, within 2 months prior to study entry Not require immunosuppressive drugs or anticoagulant therapy with heparin or warfarin for at least 2 months after study treatment No chemotherapy within 4 weeks of study entry (6 weeks for nitrosoureas)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 |
| --- | --- | --- |
| Toxicity | Serial monitoring of tumor necrosis factor alpha (TNFα) levels | up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | Sequential assessment of tumor on CT or MRI | up to 2 months | 
| IL12 level Immune response | Serum IL12 level | up to 2 months | 
| IFNγ levels Immune response | IFNγ levels | up to 2 months | 
| Immune response | 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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stage IV breast cancer, liver metastases