Breast Cancer, Solid Tumor
Conditions
Brief summary
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
Interventions
DRUGAlvespimycin
Solution, IV, 60-100 mg/m2, weekly until disease progression or DLT
DRUGTrastuzumab
Solution, IV, 2-4 mg/kg, weekly until disease progression or DLT
DRUGPaclitaxel
Solution, IV, 60-90 mg/m2, weekly until disease progression or DLT
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Dose Limiting Toxicities | During Cycle 1 (4-weeks in duration) |
Secondary
| Measure | Time frame |
|---|---|
| Summary of Clinical Laboratory Abnormalities | Weekly |
| AUC of KOS-1022 and its metabolites | Week 1 and Week 4: pretreatment, 30 and 55 minutes after start of infusion, 5, 15, 30 minutes and 1, 2, 4, 6, 24, 72 hours post-infusion; Weeks 2 and 3: pre-infusion |
| Cmax of KOS-1022 and its metabolites | Week 1 and Week 4: pretreatment, 30 and 55 minutes after start of infusion, 5, 15, 30 minutes and 1, 2, 4, 6, 24, 72 hours post-infusion; Weeks 2 and 3: pre-infusion |
| Summary of Adverse Events, Serious Adverse Events, Deaths and Discontinuations due to Adverse Events | Weekly |
| Expression of Hsp90-client proteins in peripheral blood lymphocytes | Pretreatment, 4 hours following the Day 1 KOS-1022 infusion, Day 2, Day 4; pretreatment samples Weeks 2 and 3; pretreatment, 4 hours following the Day 22 KOS-1022 infusion, Day 23, Day 25 |
| Tumor response as assessed by RECIST criteria first after two cycles of therapy | For patients with measurable disease, response will be assessed by RECIST criteria first after two cycles of therapy (8 weeks in patients having no delay in the schedule of administration) |
| T-Half of KOS-1022 and its metabolites | Week 1 and Week 4: pretreatment, 30 and 55 minutes after start of infusion, 5, 15, 30 minutes and 1, 2, 4, 6, 24, 72 hours post-infusion; Weeks 2 and 3: pre-infusion |
Countries
United States
Outcome results
None listed