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

January 31, 2017 updated by: Max Sung

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Toxicity
Time Frame: up to 15 days
Serial monitoring of tumor necrosis factor alpha (TNFα) levels
up to 15 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tumor Response
Time Frame: up to 2 months
Sequential assessment of tumor on CT or MRI
up to 2 months
IL12 level Immune response
Time Frame: up to 2 months
Serum IL12 level
up to 2 months
IFNγ levels Immune response
Time Frame: up to 2 months
IFNγ levels
up to 2 months
Immune response
Time Frame: up to 2 months
Serum antibodies (titer) to adenovirus.
up to 2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Max Sung

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Max W. Sung, MD, Icahn School of Medicine at Mount Sinai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 10, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 2, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GCO 97-779
  • MTS-GCO-97-779
  • MTS-9911-358
  • MTS-A-8200
  • CDR0000456626

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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