Gene Therapy in Treating Women With Metastatic Breast Cancer

Phase I Trial of Adenoviral Vector Delivery of the Human Interleukin-12 cDNA by Intratumoral Injection in Patents With Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: adenovirus-mediated human interleukin-12

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn Medical Center at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: adenovirus-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose	Serum antibodies (titer) to adenovirus	up to 1 month
Toxicity and safety	adverse events as assessed by NCI CTCAE v3.0	up to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response progression)	Sequential assessment of tumor on CT or MRI (complete response, partial response, stable disease, or disease)	up to 2 months
Immune response	Serum IL12, and IFNγ levels. Serum antibodies (titer) to adenovirus.	up to 2 months

Collaborators and Investigators

• Sponsor: Max Sung
• Investigators: Principal Investigator: Max W. Sung, MD, Icahn Medical Center at Mount Sinai

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: February 20, 2009
• First Submitted That Met QC Criteria: February 20, 2009
• First Posted (Estimate): February 23, 2009

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 10, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Interleukin-12
• Other Study ID Numbers: GCO 02-0797; MTS-GCO-02-0797; NIH-0707-869; CDR0000629819