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
Completed
- Conditions
- Solid TumorBreast Cancer
- Interventions
- Registration Number
- NCT00803556
- Lead Sponsor
- Bristol-Myers Squibb
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 Trastuzumab Patients whose last dose is \> 21 days prior to first dose of Trastuzumab on study. First infusion: 90 mins for 4 mg/kg loading dose of trastuzumab followed by 60 min infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of alvespimycin Patients whose last dose is \< 21 days prior to first dose of Trastuzumab on study. All infusions: 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of alvespimycin Arm 2 Trastuzumab Patients whose last dose is \> 21 days prior to first dose of Trastuzumab on study. First infusion: 90 mins for 4 mg/kg loading dose of trastuzumab followed by 60 min infusion of paclitaxel and 60 min of infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin Patients whose last dose is \< 21 days prior to first dose of Trastuzumab on study. All infusions: 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin Arm 2 Paclitaxel Patients whose last dose is \> 21 days prior to first dose of Trastuzumab on study. First infusion: 90 mins for 4 mg/kg loading dose of trastuzumab followed by 60 min infusion of paclitaxel and 60 min of infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin Patients whose last dose is \< 21 days prior to first dose of Trastuzumab on study. All infusions: 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin Arm 1 Alvespimycin Patients whose last dose is \> 21 days prior to first dose of Trastuzumab on study. First infusion: 90 mins for 4 mg/kg loading dose of trastuzumab followed by 60 min infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of alvespimycin Patients whose last dose is \< 21 days prior to first dose of Trastuzumab on study. All infusions: 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of alvespimycin Arm 2 Alvespimycin Patients whose last dose is \> 21 days prior to first dose of Trastuzumab on study. First infusion: 90 mins for 4 mg/kg loading dose of trastuzumab followed by 60 min infusion of paclitaxel and 60 min of infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin Patients whose last dose is \< 21 days prior to first dose of Trastuzumab on study. All infusions: 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin
- Primary Outcome Measures
Name Time Method Number of Dose Limiting Toxicities During Cycle 1 (4-weeks in duration)
- Secondary Outcome Measures
Name Time Method 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 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 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) Summary of Adverse Events, Serious Adverse Events, Deaths and Discontinuations due to Adverse Events Weekly Summary of Clinical Laboratory Abnormalities Weekly 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 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
Trial Locations
- Locations (2)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Indiana University Melvin & Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States