Breast Cancer, Metastatic Cancer
Conditions
Keywords
stage IV breast cancer, liver metastases
Brief summary
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
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.
Interventions
BIOLOGICALadenovirus-mediated human interleukin-12
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.
Sponsors
Max Sung
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | up to 15 days | Serial monitoring of tumor necrosis factor alpha (TNFα) levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | up to 2 months | Sequential assessment of tumor on CT or MRI |
| IL12 level Immune response | up to 2 months | Serum IL12 level |
| IFNγ levels Immune response | up to 2 months | IFNγ levels |
| Immune response | up to 2 months | Serum antibodies (titer) to adenovirus. |
Countries
United States
Outcome results
None listed