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| ID | Type | Description | Link |
|---|---|---|---|
| KDG 132 |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | 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 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alvespimycin | Drug | Solution, IV, 60-100 mg/m2, weekly until disease progression or DLT |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Dose Limiting Toxicities | During Cycle 1 (4-weeks in duration) |
| Measure | Description | Time Frame |
|---|---|---|
| Summary of Adverse Events, Serious Adverse Events, Deaths and Discontinuations due to Adverse Events | Weekly | |
| Summary of Clinical Laboratory Abnormalities | Weekly | |
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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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University Melvin & Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States | ||
| Memorial Sloan Kettering Cancer Center |
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| Trastuzumab | Drug | Solution, IV, 2-4 mg/kg, weekly until disease progression or DLT |
|
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| Paclitaxel | Drug | Solution, IV, 60-90 mg/m2, weekly until disease progression or DLT |
|
|
| 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 |
| 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 |
| 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) |
| New York |
| New York |
| 10021 |
| United States |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C448659 | 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin |
| D000068878 | Trastuzumab |
| D017239 | Paclitaxel |
| C089957 | BMS 181339 |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
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