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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Solution, IV, 60-100 mg/m2, weekly until disease progression or DLT
Solution, IV, 2-4 mg/kg, weekly until disease progression or DLT
Solution, IV, 60-90 mg/m2, weekly until disease progression or DLT
Indiana University Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Number of Dose Limiting Toxicities
Time frame: During Cycle 1 (4-weeks in duration)
Summary of Adverse Events, Serious Adverse Events, Deaths and Discontinuations due to Adverse Events
Time frame: Weekly
Summary of Clinical Laboratory Abnormalities
Time frame: Weekly
AUC of KOS-1022 and its metabolites
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
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