The purpose of this study is to determine the safety and preliminary effectiveness of ixabepilone plus lapatinib with and without capecitabine in the treatment of human epidermal growth factor receptor 2 (HER2)-positive or metastatic breast cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Lapatinib, 1000 mg, administered orally, once a day, every day, for 7 to 14 consecutive days as a lead-in period prior to the first administration of ixabepilone (Day 1). Following the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1000 mg, administered orally, once a day, every day, for a 21-day cycle.
Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1000 mg). Lapatinib, 1250 mg, administered orally once a day, every day, for 7 to 14 consecutive days as a lead-in period prior to the first administration of ixabepilone. Following the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered, 1250 mg, orally, once a day, every day, for a 21-day cycle.
The Cancer Institute Of New Jersey
New Brunswick, New Jersey, United States
Local Institution
Brisbane, Queensland, Australia
Local Institution
Modena, Italy
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Ixabepilone When Administered With Lapatinib
The MTD is defined as the maximum dose that can be administered to 6 participants such that no more than 1 (or fewer than one third if more than 6 participants receive treatment) experiences a dose-limiting toxicity (DLT), with at least 2 experiencing a DLT at the next higher dose level. The RP2D is based on the MTD and the assessment of any relevant chronic toxicities.
Time frame: Days 1 through 21
MTD and RP2D of Ixabepilone When Administered With Lapatinib Plus Capecitabine
MTD is defined as the maximum dose that can be administered to 6 participants such that no more than 1 (or fewer than one third if more than 6 participants receive treatment) experiences a DLT, with at least 2 experiencing a DLT at the next higher dose level. The RP2D is based on the MTD and the assessment of any relevant chronic toxicities.
Time frame: Days 1 through 21
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
AE=Any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical event that results in death, persistent or significant disability/incapacity, drug dependency or abuse; is life-threatening, important, a congenital anomaly/birth defect; or requires or prolongs existing hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment. Common Terminology Criteria (CTC) Grade 3=severe; Grade 4=life-threatening or disabling.
Time frame: Baseline to Day 21, continuously
Number of Participants With DLT
DLT=Any of the following events, attributable to study drug and occurring within 21 days after ixabepilone administration: Grade 3 or 4 nausea, vomiting, or diarrhea despite the use of adequate medical intervention; other Grade 3 or greater nonhematologic toxicity requiring removal from study drug; recovery from study drug-related toxicity that delayed scheduled retreatment for longer than 3 weeks; Grade 4 neutropenia for 5 or more consecutive days or Grade 3 or 4 neutropenia of any duration with sepsis or fever; thrombocytopenia or bleeding requiring platelet transfusion.
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Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1250 mg). Lapatinib, 1250 mg, administered orally once a day, every day, for 7 to 14 consecutive days as a lead-in period prior to the first administration of ixabepilone. Following the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered orally, once a day, every day, for a 21-day cycle.
Planned escalating doses of the triplet combination of ixabepilone, lapatinib, and capecitabine. No participants were enrolled in this arm due to premature termination of the study.
Time frame: Baseline to Day 21, continuously
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
CTC, Version 3.0 used to assess parameters. ULN=upper level of normal among all laboratory ranges. WBC (c/L): Grade (Gr)1:\<LLN to 3.0\*10\^9/L, Gr 2:\<3.0 to 2.0\*10\^9/L, Gr 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L; ANC (c/uL): Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L; Platelet count (c/uL): Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0\*10\^9/L; Hemoglobin (g/dL): Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL.
Time frame: Baseline and weekly from Days 1 to 21 (Cycle 1)
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
CTC, Version 3.0 used to assess parameters. ULN=upper level of normal among all laboratory ranges. ALT(U/L) Gr 1:\>ULN-2.5\*ULN,Gr 2:\>2.5-5.0\*ULN,Gr 3:\>5.0-20.0\*ULN,Gr 4:\>20.0\* ULN; AST(U/L) Gr 1:\>ULN-2.5\* ULN,Gr 2:\>2.5-5.0\*ULN,Gr 3:\>5.0-20.0\*ULN,Gr 4:\>20.0\* ULN; ALP(U/L)Gr 1:\>ULN-2.5\*ULN, Gr 2:\>2.5-5.0\*ULN, Gr 3:\>5.0-20.0\*ULN, Gr 4:\>20.0\*ULN; Creatinine (mg/dL): Gr 1:\>ULN-1.5\*ULN, Gr 2:\>1.5-3.0\*ULN, Gr 3:\>3.0-6.0\*ULN, Gr 4:\>6.0\*ULN; Total bilirubin (mg/dL): Gr 1:\>ULN-1.5\*ULN, Gr 2:\>1.5-3.0\*ULN, Gr 3:\>3.0-10.0\*ULN, Gr 4:\>10.0\*ULN
Time frame: At baseline and within 72 hours of Day 1 of 21-day cycle
Maximum Concentration of Ixabepilone
Time frame: Day 1 of 21-day cycle
Area Under the Concentration-time Curve From 0 to Infinity (AUC[INF]) and AUC From 0 to Last Quantifiable Concentration (AUC[O-T] of Ixabepilone
Time frame: Day 1 of 21-day cycle
Terminal Half-life of Ixabepilone
Time frame: Day 1 of 21-day cycle
Time to Peak Concentration of Ixabepilone
Time frame: Day 1 of 21-day cycle
Volume of Distribution at Steady State of Ixabepilone
Time frame: Day 1 of 21-day cycle
Overall Tumor Response By Number of Participants
Target lesion criteria: Complete Response(CR)=Disappearance of all clinical and radiologic evidence of target lesions; Partial Response (PR)=A 30% or greater decrease in the sum of longest diameter(LD) of all lesions in reference to the baseline sum LD. Stable Disease (SD)=Insufficient increase to qualify for Progressive Disease (PD) and insufficient shrinkage to qualify for PR; PD=A 20% or greater increase in the sum of LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline.
Time frame: Baseline and Day 21 (21-day cycle)
Duration of Response of Combination Treatment With Ixabepilone Plus Lapatinib
Duration of response is measured from the time in months that measurement criteria are first met for PR or CR, whichever is recorded first, until the date of documented PD or death. Participants who neither relapse nor die will be censored on the date of their last tumor assessment.
Time frame: First occurrence of PR or CR to PD or Death (no average, as no data available)