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

Max Sung

Status and phase: Terminated; Phase 1

Conditions: Metastatic Cancer; Breast Cancer

Treatments: Biological: adenovirus-mediated human interleukin-12

Study type: Interventional

Funder types: Other

Identifiers

NCT00301106

MTS-9911-358

MTS-GCO-97-779

CDR0000456626

MTS-A-8200

GCO 97-779

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: Female

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

adenovirus-mediated human interleukin-12

Experimental group

Description:

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.

Treatment:

Biological: adenovirus-mediated human interleukin-12