Biological Therapy in Treating Women With Stage IV Breast Cancer - Full Text View

Sponsor:	Barbara Ann Karmanos Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:	NCT00027807

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Biological: Aldesleukin Biological: Sargramostim Biological: therapeutic autologous lymphocytes	Phase I Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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/II)

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Granulocyte-macrophage colony-stimulating factor Aldesleukin Sargramostim

U.S. FDA Resources

Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:

Maximum tolerated dose [ Time Frame: The dose at which dose-limiting toxicity occurs is defined as that dose at which 2 or more of 6 patients at that dose level have their infusions stopped due to toxicities or receive less than 80% of the planned dose. ] [ Designated as safety issue: Yes ]
Toxicity profile [ Time Frame: Months 1, 2, 5 and 11, then every 6 months ] [ Designated as safety issue: Yes ]
Clinical responses [ Time Frame: Months: 1, 2, 5 and 11, then every 6 months ] [ Designated as safety issue: No ]
Overall survival and progression-free survival [ Time Frame: The interval from the beginning of immunotherapy to the time of death or for progression free survival it is defined as the interval from the beginning of immunotherapy to progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Immune changes [ Time Frame: 1 (+ 7 days), 2 (+ 7 days), 5 months (+ 7 days), then every 6months (+ 7 days) (immune evaluations will also be performed after the 4th and 8th infusion of Her2Bi armed ATC and within 1week of the completion of HER2Bi armed ATC) ] [ Designated as safety issue: No ]

Estimated Enrollment:	33
Study Start Date:	October 2001
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion.

Other Names:

Aldesleukin
Proleukin ®
IL-2

GM-CSF Injections will be given SQ GM-CSF (250 μg/m2/twice weekly), to start 3 days before the first ATC infusion and ending 1 week after the last ATC infusion.

Other Names:

LeukineTM
GM-CSF
Granulocyte-Macrophage Colony Stimulating Factor

The time for armed-ATC infusions will vary from patient to patient, but the dose of armed-ATC (up to 40 billion) will be given over 30 min.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Phase I:

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

PATIENT CHARACTERISTICS:

Age:

18 and over

Sex:

Female

Menopausal status:

Not specified

Performance status:

Karnofsky 70-100% OR
ECOG 0-2

Life expectancy:

At least 3 months

Hematopoietic:

Granulocyte count at least 1,500/mm^3
Platelet count at least 50,000/mm^3
Hemoglobin at least 8 g/dL

Hepatic:

Bilirubin less than 1.5 times normal
SGOT less than 1.5 times normal

Renal:

Creatinine no greater than 1.8 mg/dL
Creatinine clearance at least 60 mL/min
BUN no greater than 1.5 times normal

Cardiovascular:

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

Other:

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 participation
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

Chemotherapy:

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

Surgery:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027807

Locations

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

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Lawrence G. Lum, MD, DSc

Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Grabert RC, Smith JA, Tiggs JC, et al.: Anti-CD3 activated T cells (ATC) armed with OKT3 x Herceptin Bispecific antibody (Her2Bi), survive and divide, and secrete cytokines and chemokines after multiple cycles of killing directed at Her2/neu+ (Her2) tumor targets. [Abstract] Proceedings of the 94th Annual Meeting of the American Association of Cancer Research 44: A-2872, 565, 2003.

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.

Sen M, Wankowski DM, Garlie NK, Siebenlist RE, Van Epps D, LeFever AV, Lum LG. Use of anti-CD3 x anti-HER2/neu bispecific antibody for redirecting cytotoxicity of activated T cells toward HER2/neu+ tumors. J Hematother Stem Cell Res. 2001 Apr;10(2):247-60.

Responsible Party:	Lawrence G. Lum, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:	NCT00027807 History of Changes
Other Study ID Numbers:	CDR0000069072, P30CA022453, WSU-2006-130, RWMC-0635146, WSU-010307M1F, WSU-0312004412
Study First Received:	December 7, 2001
Last Updated:	November 1, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:

stage IV breast cancer
recurrent breast cancer
ductal breast carcinoma

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aldesleukin
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 12, 2012