Patient case: 74-year-old female with melanoma; genetic feature: no tumor infiltrating lymphocytes

Clinical trial: Biological Therapy in Treating Women With Stage IV Breast Cancer

Summary: 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.

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.
  PLEASE NOTE: THIS STUDY WAS INTENDED TO BE A PHASE I/II STUDY, BUT NEVER MOVED FORWARD TO PHASE II. (4-22-09)

Eligibility: 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

Relevance to patient case: not relevant