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Biological Therapy in Treating Women With Stage IV Breast Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
First Received: December 7, 2001   Last Updated: February 6, 2009   History of Changes
Sponsor: Barbara Ann Karmanos Cancer Institute
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
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: 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:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Toxicity profile [ Designated as safety issue: Yes ]
  • Clinical responses [ Designated as safety issue: No ]
  • Overall survival and progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immune changes [ Designated as safety issue: No ]

Estimated Enrollment: 63
Study Start Date: October 2001
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
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 Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute     313-576-9363        
Sinai-Grace Hospital Recruiting
Detroit, Michigan, United States, 48235
Contact: Lawrence Lum     313-576-8326        
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Lawrence G. Lum, MD, DSc Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
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: Barbara Ann Karmanos Cancer Institute ( Lawrence G. Lum )
Study ID Numbers: CDR0000069072, WSU-2006-130, RWMC-0635146, WSU-010307M1F, WSU-0312004412
Study First Received: December 7, 2001
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00027807     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer
ductal breast carcinoma

Additional relevant MeSH terms:
Anti-Infective Agents
Anti-HIV Agents
Skin Diseases
Antineoplastic Agents
Breast Neoplasms
Antiviral Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Aldesleukin
Anti-Retroviral Agents
Therapeutic Uses
Breast Diseases

ClinicalTrials.gov processed this record on November 30, 2009