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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Toxicity
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- Female
- Accepts 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:
- •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)
Exclusion Criteria
- Not provided
Arms & Interventions
adenovirus-mediated human interleukin-12
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.
Intervention: adenovirus-mediated human interleukin-12 (Biological)
Outcomes
Primary Outcomes
Toxicity
Time Frame: up to 15 days
Serial monitoring of tumor necrosis factor alpha (TNFα) levels
Secondary Outcomes
- Tumor Response(up to 2 months)
- IFNγ levels Immune response(up to 2 months)
- Immune response(up to 2 months)
- IL12 level Immune response(up to 2 months)
Investigators
Max Sung
Associate Professor
Icahn School of Medicine at Mount Sinai