Combination Chemotherapy Plus Biological Therapy in Treating Patients With Stage II or Stage III Breast Cancer - Full Text View

Sponsor:	Roger Williams Medical Center
Information provided by:	Roger Williams Medical Center
ClinicalTrials.gov Identifier:	NCT00022230

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Biological: aldesleukin Biological: filgrastim Biological: sargramostim Biological: therapeutic autologous lymphocytes Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel	Phase I Phase II

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	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)

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Paclitaxel Granulocyte-macrophage colony-stimulating factor Aldesleukin Filgrastim Sargramostim Lenograstim Granulocyte colony-stimulating factor

U.S. FDA Resources

Further study details as provided by Roger Williams Medical Center:

Primary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Disease-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Immune functions [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	January 2000
Estimated Study Completion Date:	January 2007
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

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

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 greater than 8 g/dL

Hepatic:

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

Renal

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

Cardiovascular:

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

Pulmonary:

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

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

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

Radiotherapy:

Not specified

Surgery:

Prior complete resection of tumor allowed

Other:

Prior successful neoadjuvant therapy allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00022230

Locations

United States, Rhode Island
Roger Williams Medical Center
Providence, Rhode Island, United States, 02908-4735

Sponsors and Collaborators

Roger Williams Medical Center

Investigators

Study Chair:

Lawrence G. Lum, MD, DSc

Roger Williams Medical Center

More Information

No publications provided

Responsible Party:	Lawrence Lum, Roger Williams Medical Center
ClinicalTrials.gov Identifier:	NCT00022230 History of Changes
Other Study ID Numbers:	CDR0000068797, RWMC-0633846
Study First Received:	August 10, 2001
Last Updated:	August 9, 2011
Health Authority:	United States: Federal Government

Keywords provided by Roger Williams Medical Center:

stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Aldesleukin
Doxorubicin
Paclitaxel
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents

Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic
Adjuvants, Immunologic
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on February 12, 2012