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Biological Therapy in Treating Women With Stage IV Breast Cancer

Information source: Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Breast Cancer

Intervention: Aldesleukin (Biological); Sargramostim (Biological); therapeutic autologous lymphocytes (Biological)

Phase: Phase 1

Status: Completed

Sponsored by: Barbara Ann Karmanos Cancer Institute

Official(s) and/or principal investigator(s):
Lawrence G. Lum, MD, DSc, Study Chair, Affiliation: Barbara Ann Karmanos Cancer Institute


RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining different types of biological therapies may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining different biological therapies in treating women who have stage IV breast cancer.

Clinical Details

Official title: Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (Phase I Only as of 4-22-09 as Per IRB Approval Date)

Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Maximum tolerated dose

Toxicity profile

Clinical responses

Overall survival and progression-free survival

Secondary outcome: Immune changes

Detailed description: OBJECTIVES:

- Determine the maximum tolerated dose of armed activated T cells given in combination

with interleukin-2 and sargramostim (GM-CSF) in women with stage IV breast cancer.

- Determine the toxicity profile of this regimen in these patients.

- Determine the clinical response and overall and progression-free survival of patients

treated with this regimen. OUTLINE: This is a dose-escalation study of armed activated T cells. Patients undergo peripheral blood mononuclear cell (PBMC) collection. The PBMCs are treated ex vivo with monoclonal antibody OKT3 to form armed activated T cells (ATC). The armed ATC are expanded for 14 days in interleukin-2 (IL-2). Patients receive armed ATC IV over 30 minutes twice weekly for 4 weeks. Patients also receive IL-2 subcutaneously (SC) once daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first infusion of armed ATC and continuing until 7 days after the last infusion of armed ATC. Cohorts of 3-6 patients receive escalating doses of armed ATC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at that dose. Patients are followed at 1, 2, and 5 months and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for the phase I portion of this study and a total of 18-33 patients will be accrued for the phase II portion of this study within 4-6 years. PLEASE NOTE: THIS STUDY WAS INTENDED TO BE A PHASE I/II STUDY, BUT NEVER MOVED FORWARD TO PHASE II. (4-22-09)


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.



- Histologically confirmed infiltrating ductal carcinoma of the breast

- Metastatic disease

- Clinically asymptomatic with non-life-threatening metastases allowed

- Measurable or evaluable disease by radiograph, CT scan, MRI, nuclear medicine bone

scan, or physical examination

- No measurable disease allowed if tumor or metastasis has been removed or

successfully treated prior to study

- No rapidly progressive symptomatic disease affecting major organ systems (e. g., lungs

and liver)

- Stable or unstable disease for 3 months on hormonal therapy

- Stable or unstable disease for at least 1 month after chemotherapy

- No active brain metastases

- Brain metastases previously treated with definitive radiotherapy and/or surgical

resection allowed

- Hormone receptor status:

- Estrogen and progesterone receptor status known

Phase II:

- All Phase I criteria

- HER2/neu overexpression (2+ or 3+) by immunohistochemistry

- Prior trastuzumab (Herceptin) allowed if disease still overexpresses HER2/neu


- 18 and over


- Female

Menopausal status:

- Not specified

Performance status:

- Karnofsky 70-100% OR

- ECOG 0-2

Life expectancy:

- At least 3 months


- Granulocyte count at least 1,500/mm^3

- Platelet count at least 50,000/mm^3

- Hemoglobin at least 8 g/dL


- Bilirubin less than 1. 5 times normal

- SGOT less than 1. 5 times normal


- Creatinine no greater than 1. 8 mg/dL

- Creatinine clearance at least 60 mL/min

- BUN no greater than 1. 5 times normal


- No myocardial infarction within the past year

- No prior myocardial infarction with coronary symptoms requiring medication and/or

depressed left ventricular function (LVEF less than 50% by MUGA)

- No angina or coronary symptoms requiring medication and/or with depressed left

ventricular function (LVEF less than 50% by MUGA)

- No congestive heart failure requiring medical management

- LVEF at least 50% at rest by MUGA

- No uncontrolled hypertension (i. e., systolic blood pressure [BP] ≥ 130 mm Hg or

diastolic BP ≥ 80 mm Hg) Pulmonary:

- FEV1, DLCO, and FVC at least 50% predicted


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No other serious medical or psychiatric illness that would preclude study


- No other prior or concurrent malignancy within the past 5 years except curatively

treated squamous cell carcinoma in situ of the cervix, basal cell skin cancer, or any other curatively treated disease in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy:

- See Disease Characteristics

- Prior trastuzumab allowed for phase I


- See Disease Characteristics

- At least 4 weeks since prior chemotherapy

Endocrine therapy:

- See Disease Characteristics

- Concurrent hormonal therapy for breast cancer must continue during study

- No other concurrent hormonal therapy except steroids for adrenal failure, septic

shock, or pulmonary toxicity or hormonal therapy for non-disease-related conditions (e. g., insulin for diabetes) Radiotherapy:

- See Disease Characteristics


- See Disease Characteristics

Locations and Contacts

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Related publications:

Lum LG, Rathore R, Colvin GA, et al.: Targeting HER2/neu tumor cells with anti-CD3 activated T cells: clinical trials and trafficking studies. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-719, 2003.

Starting date: October 2001
Last updated: August 17, 2015

Page last updated: August 23, 2015

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