Clinical trial NCT00634088: Phase I Study of Ixabepilone Plus Lapatinib With or Without Capecitabine in the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Breast Cancer
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2008-03-12
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Ixabepilone When Administered With Lapatinib
timeFrame: Days 1 through 21
measure: MTD and RP2D of Ixabepilone When Administered With Lapatinib Plus Capecitabine
timeFrame: Days 1 through 21
Secondary outcomes:
measure: 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)
timeFrame: Baseline to Day 21, continuously
measure: Number of Participants With DLT
timeFrame: Baseline to Day 21, continuously
measure: Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
timeFrame: Baseline and weekly from Days 1 to 21 (Cycle 1)
measure: Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
timeFrame: At baseline and within 72 hours of Day 1 of 21-day cycle
measure: Maximum Concentration of Ixabepilone
timeFrame: Day 1 of 21-day cycle
measure: 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
timeFrame: Day 1 of 21-day cycle
measure: Terminal Half-life of Ixabepilone
timeFrame: Day 1 of 21-day cycle
measure: Time to Peak Concentration of Ixabepilone
timeFrame: Day 1 of 21-day cycle
measure: Volume of Distribution at Steady State of Ixabepilone
timeFrame: Day 1 of 21-day cycle
measure: Overall Tumor Response By Number of Participants
timeFrame: Baseline and Day 21 (21-day cycle)
measure: Duration of Response of Combination Treatment With Ixabepilone Plus Lapatinib
timeFrame: First occurrence of PR or CR to PD or Death (no average, as no data available)
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: The Cancer Institute Of New Jersey
state: New Jersey
city: Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Modena
country: Italy
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: