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Biological Therapy in Treating Women With Stage IV Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00027807
First received: December 7, 2001
Last updated: November 1, 2011
Last verified: November 2011
History of Changes
  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 1
Phase 2

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:

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:
    Biological: Aldesleukin
    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
    Biological: Sargramostim
    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
    Biological: therapeutic autologous lymphocytes
    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.

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 June 18, 2013