Parallel Phase I Study of Ixabepilone Plus Lapatinib and Ixabepilone Plus Lapatinib Plus Capecitabine in Subjects With HER2 Positive Locally Advanced or Metastatic Breast Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 13
- Locations
- 2
- Primary Endpoint
- MTD and RP2D of Ixabepilone When Administered With Lapatinib Plus Capecitabine
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Females aged 18 years or older with histologic or cytologic diagnosis of adenocarcinoma originating in the breast
- •Radiologic or pathologic evidence that the cancer is metastatic or locally advanced (a T4 tumor and stage IIIB/IIIC disease) and not curable by local measures, such as radiation or surgery
- •Positive status for human epidermal growth factor receptor 2
- •Measurable disease as per Response Evaluation Criteria In Solid Tumors guidelines
- •Karnofsky performance status of 70 to 100
- •Life expectancy of at least 3 months
Exclusion Criteria
- •Prior radiation must not have included 30% or more of major bone-marrow containing areas, such as the pelvis and lumbar spine
- •Common Terminology Criteria Grade 2 or greater neuropathy
- •Inadequate hematologic, hepatic, or renal function
- •Known prior severe hypersensitivity reactions to agents containing Cremophor® EL or known hypersensitivity or prior intolerance to fluoropyrimidine
- •Known or suspected dihydropyrimidine dehydrogenase deficiency
- •More than 3 prior chemotherapy regimens in the metastatic setting
- •Prior treatment with an epothilone or lapatinib; prior treatment with capecitabine within the past 6 months
Arms & Interventions
Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg
Dose Level 1
Intervention: Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg (Drug)
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg
Dose Level 2
Intervention: Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg (Drug)
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg
Dose Level 3
Intervention: Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg (Drug)
Ixabepilone + Lapatinib + Capecitabine
Triplet Combination
Intervention: Ixabepilone + Lapatinib + Capecitabine (Drug)
Outcomes
Primary Outcomes
MTD and RP2D of Ixabepilone When Administered With Lapatinib Plus Capecitabine
Time Frame: Days 1 through 21
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.
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Ixabepilone When Administered With Lapatinib
Time Frame: Days 1 through 21
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.
Secondary Outcomes
- Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade(Baseline and weekly from Days 1 to 21 (Cycle 1))
- Maximum Concentration of Ixabepilone(Day 1 of 21-day cycle)
- Volume of Distribution at Steady State of Ixabepilone(Day 1 of 21-day cycle)
- Duration of Response of Combination Treatment With Ixabepilone Plus Lapatinib(First occurrence of PR or CR to PD or Death (no average, as no data available))
- 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)(Baseline to Day 21, continuously)
- Number of Participants With DLT(Baseline to Day 21, continuously)
- Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade(At baseline and within 72 hours of Day 1 of 21-day cycle)
- Time to Peak Concentration of Ixabepilone(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(Day 1 of 21-day cycle)
- Terminal Half-life of Ixabepilone(Day 1 of 21-day cycle)
- Overall Tumor Response By Number of Participants(Baseline and Day 21 (21-day cycle))