The purpose of this study is to determine the maximum tolerated dose, dose-limiting toxicity, and recommended Phase II dose of ixabepilone in combination with carboplatin in patients with non-small cell lung cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
On Day 1 of each 21-day cycle, ixabepilone, 32 mg/m\^2, intravenous (IV) solution administered as a 3-hour infusion; 30 minutes after the end of ixabepilone infusion, carboplatin, 5 mg/min/mL, intravenous IV solution infused over 30 minutes. Repeated once every 3 weeks, for a maximum of 6 cycles.
After all participants in Dose Level 1 (ixabepilone, 32 mg/m\^2 + carboplatin, 5 mg/min/mL) have been observed for 1 full 21-day cycle, Dose Level 2(ixabepilone, 32 mg/m\^2 + carboplatin, 6 mg/min/mL) opened. On Day 1 of each 21-day cycle, ixabepilone, 32 mg/m\^2, IV solution administered as a 3-hour infusion; 30 minutes after the end of ixabepilone infusion, carboplatin, 6 mg/min/mL, IV solution infused over 30 minutes. Repeated once every 3 weeks, for a maximum of 6 cycles.
Local Institution
Chuo-Ku, Tokyo, Japan
Number of Participants With Dose-limiting Toxicity (DLT)
DLT is defined as any of the following: Common Terminology Criteria (CTC), Version 3, Grade(Gr) 4 neutropenia (absolute neutrophil count \<500 cells/mm\^3) for at least 5 days or febrile neutropenia; Gr 4 thrombocytopenia (\<25,000 cells/mm\^3 or bleeding needing platelet transfusion); Gr 3 or 4 nausea, vomiting, or diarrhea, despite medical intervention; any other drug-related Gr 3 or 4 nonhematologic toxicity, except Gr 3 injection site reaction, fatigue/asthenia, transient arthralgia/myalgia, or transient electrolytes abnormal. Gr 1=Mild; Gr 2=Moderate; Gr 3=Severe; Gr 4=Life-threatening.
Time frame: Days 1 through 21 (Cycle 1)
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose of Carboplatin in Combination With Ixabepilone, 32 mg/m^2
The MTD was defined as the highest dose evaluated for which less than one sixth of patients experience a DLT in Cycle 1. The recommended phase 2 dose is the MTD defined in Cycle 1, with consideration given to chronic cumulative toxicity occurring at later cycles.
Time frame: Days 1 through 21 (Cycle 1)
Number of Participants With Death as Outcome, Treatment-related Serious Adverse Events (SAEs), SAEs, Adverse Events (AEs), and Treatment-related AEs Leading to Discontinuation
An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires inpatient hospitalization or prolongs existing hospitalization. An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. Treatment-related comprises certainly, probably, and possibly related and of unknown relationship to study drug.
Time frame: Days 1 through 21 (Cycle 1)
Number of Participants With Grade 3 or Greater Treatment-related AEs
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. AEs graded according to CTC, Version 3.0. Gr 1=Mild; Gr 2=Moderate; Gr 3=Severe; Gr 4=Life-threatening. Treatment-related comprises certainly, probably, and possibly related and of unknown relationship to study drug.
Time frame: Days 1 through 21 (Cycle 1)
Number of Participants With Abnormalities in Hematology Laboratory Values by Worst CTC Grade
LLN=lower level of normal; ULN=upper level of normal. Hemoglobin (g/dL; LLN=11.3; ULN=14.9); leukocytes (\*10\^3 c/uL; LLN=4.1; ULN=6.1); lymphocytes (\*10\^3 c/uL); neutrophils (absolute), neutrophils + bands (\*10\^3 c/uL); platelet count (\*10\^9 c/L; LLN=131; ULN=365) Appendix 7.1.2
Time frame: At screening and Days 8 and 15 of Cycle 1 (21 days)
Number of Participants With Abnormalities in Serum Chemistry Laboratory Values by Worst CTC Grade
ULN=upper limit of normal; LLN=lower limit of normal. Alkaline phosphatase=ALP(LLN=115; ULN=359) (U/L); alanine aminotransferase=ALT (LLN=8; ULN=42)(U/L); aspartate aminotransferase=AST (LLN=13; ULN=33) (U/L); albumin (LLN=3.7; ULN=5.2)(g/dL); bilirubin (LLN=0.3; ULN=1.2)(mg/dL); calcium (LLN=8.7; ULN=10.3)(mg/dL); creatinine (LLN=0.6; ULN=1.1)(mg/dL); potassium (LLN=3.6; ULN=4.9) (mEq/L); sodium (LLN=138; ULN=146) (mEq/L)
Time frame: At screening and Days 8 and 15 of Cycle 1 (21 days)
Number of Participants With Abnormalities in Urine Testing Results by Worst CTC Grade
Toxicities graded according to CTC, Version 3. Protein Gr 1: \<1.0 g/24 hrs (1+); Gr 2: 1.0 to 3.4 g/24 hrs (2+ to 3+ ); Gr 3: \>=3.5 g/24 hrs (4+); Gr 4: Nephrotic syndrome. Note: + = qualitative measure of urine chemistry.
Time frame: At screening and Days 8 and 15 of Cycle 1 (21 days)
Number of Participants With Abnormalities in Blood Pressure and Heart Rate
Blood pressure and heart rate obtained before ixabepilone infusion, every 1 hour during and at the end of ixabepilone infusion, and at the end of carboplatin infusion in Cycle 1. For subsequent cycles, vital signs obtained before ixabepilone infusion, at the end of ixabepilone infusion, and at the end of carboplatin infusion. Any new or worsening clinically significant changes since last entry were recorded as appropriate AE or SAE.
Time frame: At screening and Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (Study day 22)
Number of Participants With Abnormalities in Weight and Eastern Cooperative Oncology Group (ECOG) Performance Status
Participants weighed same day as serum chemistry tests. Body surface area recalculated only if body weight changes \>10%. ECOG criteria used to assess disease progression and affects on daily living abilities and to determine appropriate treatment and prognosis. Grade 1=Restricted physical activity but ambulatory and capable of light work; Grade 2=Ambulatory, capable of self care, but unable to carry out any work activities; Grade 3=Capable of limited self care, confined to bed or chair 50% or more of waking hours; Grade 4=Completely disabled, totally confined to bed or chair.
Time frame: At screening of Cycle 1 (21 days) and Day 1 of Cycle 2 (Study day 22)
Number of Participants at Each Response Evaluation Criteria in Solid Tumors (RECIST) Assessment
Tumor response was assessed using the RECIST assessment: Complete response (CR)=Disappearance of all clinical and radiologic evidence of target lesions; Partial response (PR)=At least 30% reduction in the sum of the longest diameters of all target lesions; Progressive disease (PD)=At least 20% increase in the sum of the longest diameters of all target lesions; Stable disease (SD)=Neither PR nor PD criteria were met.
Time frame: Days 1 through 21 (Cycle 1)
Maximum Observed Plasma Concentration of Ixabepilone
Time frame: Days 1 to 8 of Cycle 1 (21 days)
Time of Maximum Observed Plasma Concentration of Ixabepilone
Time frame: Days 1 to 8 of Cycle 1 (21 days)
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time of Ixabepilone
Time frame: Days 1 to 8 of Cycle 1 (21 days)
Volume of Distribution at Steady State of Ixabepilone
Time frame: Days 1 to 8 of Cycle 1 (21 days)
Total Body Clearance of Ixabepilone
Time frame: Days 1 to 8 of Cycle 1 (21 days)