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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

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
Toxicity	Serial monitoring of tumor necrosis factor alpha (TNFα) levels	up to 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	Sequential assessment of tumor on CT or MRI	up to 2 months
IL12 level Immune response	Serum IL12 level	up to 2 months
IFNγ levels Immune response	IFNγ levels	up to 2 months
Immune response	Serum antibodies (titer) to adenovirus.	up to 2 months

Collaborators and Investigators

• Sponsor: Max Sung
• Investigators: Study Chair: Max W. Sung, MD, ICAHN School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: March 8, 2006
• First Submitted That Met QC Criteria: March 8, 2006
• First Posted (Estimate): March 10, 2006

Study Record Updates

• Last Update Posted (Estimate): February 2, 2017
• Last Update Submitted That Met QC Criteria: January 31, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: stage IV breast cancer; liver metastases
• 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 97-779; MTS-GCO-97-779; MTS-9911-358; MTS-A-8200; CDR0000456626