Gene Therapy in Treating Women With Metastatic Breast Cancer

Max Sung

Status and phase: Completed; Phase 1

Conditions: Breast Cancer

Treatments: Biological: adenovirus-mediated human interleukin-12

Study type: Interventional

Funder types: Other

Identifiers

NCT00849459

NIH-0707-869

CDR0000629819

GCO 02-0797

MTS-GCO-02-0797

Details and patient eligibility

About

RATIONALE: Placing the gene for interleukin-12 into breast cancer cells may help the body build an immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gene therapy in treating women with metastatic breast cancer.

Full description

OBJECTIVES:

• Determine the toxicity and maximum tolerated dose of intratumoral injection of adenovirus-mediated human interleukin-12 gene in women with metastatic breast cancer.
• Determine the tumor response in patients treated with this regimen.
• Determine the immune response in patients treated with this regimen.

OUTLINE: Patients receive a single dose of adenovirus-mediated human interleukin-12 intratumorally via percutaneous needle placement under ultrasound guidance.

Blood and tumor tissue samples are collected periodically for immunological laboratory studies. Samples are analyzed for serum cytokine levels by ELISA; qualitative analysis of immune biomarkers by IHC staining; and immune cell biomarker analysis by FACS.

After completion of study therapy, patients are followed periodically.

Enrollment: 3 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic adenocarcinoma of the breast

  • Malignant disease in the skin, chest wall, or other sites (lymph nodes or primary tumor in the breast) accessible to percutaneous needle placement and injection

    • Solitary or multiple tumors
    • Measurable disease in ≥ 2 dimensions by physical examination or CT/MRI scan
    • Malignant tumors in the skin and chest wall must be ≥ 4 mm in diameter by physical examination
    • Malignant tumors in other accessible sites must be ≥ 1 cm in diameter on physical examination

  • Malignant disease in other organs (in addition to skin or chest wall metastases) allowed

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• Karnofsky performance status 70-100%

• Life expectancy ≥ 16 weeks

• Granulocyte count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9.0 mg/dL

• PT normal

• Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 45 mL/min

• Serum total bilirubin ≤ 2.0 times upper limit of normal (ULN)

• Serum transaminases ≤ 2.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Weight ≥ 30 kg (for patients treated with the highest dose level of study drug)

• No active infection or concurrent serious medical illness

• No HIV positivity

• No other malignancy within the past 5 years except for the following:

  • Inactive nonmelanoma skin cancer
  • In situ carcinoma of the cervix
  • Grade 1 papillary bladder cancer

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No anticoagulant therapy with heparin or warfarin for ≥ 2 months after completion of study treatment

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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3 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