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

• Sponsor: Max Sung (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00301106
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Metastatic Cancer	Biological: adenovirus-mediated human interleukin-12	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Toxicity [up to 15 days]

   Serial monitoring of tumor necrosis factor alpha (TNFα) levels

Secondary Outcome Measures

1. Tumor Response [up to 2 months]

   Sequential assessment of tumor on CT or MRI

2. IL12 level Immune response [up to 2 months]

   Serum IL12 level

3. IFNγ levels Immune response [up to 2 months]

   IFNγ levels

4. Immune response [up to 2 months]

   Serum antibodies (titer) to adenovirus.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Medical Center	New York	New York	United States	10029

Sponsors and Collaborators

• Max Sung

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Max Sung, Associate Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT00301106
• Other Study ID Numbers: GCO 97-779; MTS-GCO-97-779; MTS-9911-358; MTS-A-8200; CDR0000456626
• First Posted: Mar 10, 2006
• Last Update Posted: Feb 2, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Max Sung, Associate Professor, Icahn School of Medicine at Mount Sinai: stage IV breast cancer; liver metastases
• Additional relevant MeSH terms: Breast Neoplasms; Interleukin-12

Study Results

No Results Posted as of Feb 2, 2017