Combination Chemotherapy Plus Biological Therapy in Treating Patients With Stage II or Stage III Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00022230
Recruitment Status : Withdrawn (PI left Institution)
First Posted : January 27, 2003
Last Update Posted : May 5, 2015
Information provided by:
Roger Williams Medical Center

August 10, 2001
January 27, 2003
May 5, 2015
January 2000
January 2007   (Final data collection date for primary outcome measure)
  • Toxicity
  • Disease-free survival
  • Overall survival
  • Immune functions
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Complete list of historical versions of study NCT00022230 on Archive Site
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Combination Chemotherapy Plus Biological Therapy in Treating Patients With Stage II or Stage III Breast Cancer
Combination of Chemotherapy With Taxol, Adriamycin, and Cytoxan (TAC), Multiple Infusions of Activated T Cells (ATC), Interleukin-2 (IL-2) and GM-CSF for High Risk Breast Cancer With and Without Her2/Neu Overexpression. (Phase I/II)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Combining chemotherapy with biological therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of giving chemotherapy together with biological therapy and to see how well they work in treating patients with stage II or stage III breast cancer.


  • Determine the toxic effects of sequential paclitaxel (or other taxane), doxorubicin, and cyclophosphamide followed by immunotherapy with activated T cells, interleukin-2, and sargramostim (GM-CSF) in patients with high-risk stage II or III breast cancer.
  • Determine the disease-free survival and overall survival of patients treated with this regimen.
  • Determine the immune function of patients treated with this regimen.

OUTLINE: Patients are stratified according to number of positive lymph nodes (less than 4 nodes vs 4-9 nodes vs 10 or more nodes), type of taxane chemotherapy during study (paclitaxel vs other taxane), and prior treatment with 2 of 3 study chemotherapy agents (yes vs no).

Patients receive doxorubicin IV on day 1 and filgrastim (G-CSF) on days 3-10 of 3 consecutive 14-day courses. Patients then receive paclitaxel or another taxane IV on day 1 and G-CSF on days 3-10 of 3 consecutive 14-day courses. Patients then receive cyclophosphamide IV on day 1 and G-CSF on days 3-10 of 3 consecutive 14-day courses. Patients who enroll after previously receiving 2 of these 3 chemotherapy drugs may receive the third. Treatment continues in the absence of disease progression or unacceptable toxicity.

After recovery from chemotherapy, patients undergo peripheral blood mononuclear cell (PBMC) collection. The PBMC are treated ex vivo with monoclonal antibody OKT3 to form activated T cells (ATC). The ATC are expanded for up to 14 days in interleukin-2 (IL-2).

At 3-4 weeks after PBMC collection, patients receive ATC IV over 15-30 minutes weekly for 8 weeks. Patients also receive IL-2 subcutaneously (SC) daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first ATC infusion and continuing until 7 days after completion of ATC therapy.

Patients are followed every 3 months for 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 40-60 patients will be accrued for this study within 4-5 years.

Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Breast Cancer
  • Biological: aldesleukin
  • Biological: filgrastim
  • Biological: sargramostim
  • Biological: therapeutic autologous lymphocytes
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: paclitaxel
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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January 2007
January 2007   (Final data collection date for primary outcome measure)


  • Histologically confirmed stage II or III adenocarcinoma of the breast
  • High-risk disease

    • At least 4 positive lymph nodes
    • Fewer than 4 positive lymph nodes considered high-risk if one of the following is present:

      • HER2/neu-positive disease
      • Enlarged axillary nodes
      • Extra capsular extension of tumor from lymph node
      • Dermal lymphatic invasion
      • Vascular invasion
      • Bilateral disease
      • Familial breast cancer
      • T4 locally advanced disease
  • Clinically chemosensitive to prior paclitaxel (or other taxane), doxorubicin, and cyclophosphamide

    • No relapse after chemotherapy
  • No clinical evidence of brain metastases
  • Hormone receptor status:

    • Estrogen and progesterone receptor status known



  • 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 greater than 8 g/dL


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


  • Creatinine less than 1.8 mg/dL
  • Creatinine clearance at least 60 mL/min
  • BUN less than 1.5 times normal


  • Ejection fraction at least 45% by MUGA
  • No uncontrolled or significant cardiovascular disease
  • No myocardial infarction within the past year
  • No significant congestive heart failure


  • FEV_1 at least 60% predicted
  • DLCO at least 60% predicted
  • FVC at least 60% predicted


  • No other malignancy except curatively treated squamous cell carcinoma in situ of the cervix or basal cell skin cancer
  • No other serious medical or psychiatric illness that would preclude study participation
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy:

  • Not specified


  • See Disease Characteristics
  • Prior standard chemotherapy with anthracyclines or combination chemotherapy involving a combination of taxanes, doxorubicin, and/or cyclophosphamide allowed

Endocrine therapy:

  • No concurrent hormonal therapy for breast cancer
  • Concurrent hormonal therapy for nondisease-related conditions (e.g., insulin for diabetes) allowed
  • Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed


  • Not specified


  • Prior complete resection of tumor allowed


  • Prior successful neoadjuvant therapy allowed
Sexes Eligible for Study: Female
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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Lawrence Lum, Roger Williams Medical Center
Roger Williams Medical Center
Not Provided
Study Chair: Lawrence G. Lum, MD, DSc Roger Williams Medical Center
Roger Williams Medical Center
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP