Clinical Trial of the Combination of Intravenous Alvespimycin (KOS-1022), Trastuzumab With or Without Paclitaxel in Patients With Advanced Solid Tumor Malignancies or Her2 Positive Metastatic Breast Cancer Who Have Previously Failed Trastuzumab Therapy

Phase 1 Clinical Trial of the Combination of Intravenous Alvespimycin (KOS-1022), Trastuzumab With or Without Paclitaxel

To determine the Maximally Tolerable Dose (MTD) of KOS-1022 when administered weekly in combination with trastuzumab or in combination with trastuzumab and paclitaxel to patients with advanced solid tumor malignancies

Inclusion Criteria:

• KPS performance status >= 70%

• Schedule A: all patients must have a histologically confirmed solid tumor malignancy. Schedule B: patients must have metastatic breast cancer with Her2 amplification by FISH or 3+ Her2 overexpression by immunohistochemistry ("IHC"). Patients are not required to have measurable disease for this investigation. Disease must be assessed within 28 days prior to treatment initiation

• All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to NCI CTCAE (v. 3.0) Grade <= 2 (except for alopecia)

• The following laboratory results, within 10 days of KOS-1022 administration:

  • Hemoglobin >= 8.5 g/dL
  • Absolute neutrophils count >= 1.5 x 10*9* /L
  • Platelet count >= 75 x 10*9*/L
  • Serum bilirubin <= 2 x ULN
  • AST and ALT <= 2.5 x ULN
  • Serum creatinine <= 2 x ULN

Exclusion Criteria:

• Documented hypersensitivity reaction of CTCAE Grade >= 3 to prior therapy containing trastuzumab
• Pregnant or breast-feeding women. Male patients must be surgically sterile or agree to use an acceptable method of contraception
• Known active CNS metastases
• Administration of any other chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 14 days prior to receipt of study medication. Patients should be 6 weeks from last dose of nitrosourea
• Patients with Grade 2 or higher dyspnea at rest on room air; patients with other clinically significant pulmonary co-morbidity(s) that might predispose the patient to pulmonary toxicity
• Moderately severe dry eye
• Prior pulmonary toxic chemotherapy (e.g, bleomycin or carmustine)
• Congestive heart failure, or a left ventricular ejection fraction (LVEF)
• Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient
• Patients with previous malignancies unless free of recurrence for at least 5 years except cured basal cell carcinoma of the skin, carcinoma-in-situ of either the uterine cervix or urinary bladder