Clinical trial NCT00301106: Biological Therapy in Treating Women With Breast Cancer That Has Spread to the Liver
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Metastatic Cancer
Keywords: stage IV breast cancer
liver metastases
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2006-03-10
Enrollment: 2
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Toxicity
timeFrame: up to 15 days
Secondary outcomes:
measure: Tumor Response
timeFrame: up to 2 months
measure: IL12 level Immune response
timeFrame: up to 2 months
measure: IFNγ levels Immune response
timeFrame: up to 2 months
measure: Immune response
timeFrame: up to 2 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Max W. Sung, MD
role: STUDY_CHAIR
References: