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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00634088




Registration number
NCT00634088
Ethics application status
Date submitted
5/03/2008
Date registered
12/03/2008
Date last updated
10/03/2016

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
EURDRACT: 2007-004123-38
Secondary ID [2] 0 0
CA163-144
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg
Treatment: Drugs - Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg
Treatment: Drugs - Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg
Treatment: Drugs - Ixabepilone + Lapatinib + Capecitabine

Experimental: Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg - Dose Level 1

Experimental: Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg - Dose Level 2

Experimental: Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg - Dose Level 3

Experimental: Ixabepilone + Lapatinib + Capecitabine - Triplet Combination


Treatment: Drugs: Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg
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.

Treatment: Drugs: Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg
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.

Treatment: Drugs: Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg
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.

Treatment: Drugs: Ixabepilone + Lapatinib + Capecitabine
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Ixabepilone When Administered With Lapatinib
Timepoint [1] 0 0
Days 1 through 21
Primary outcome [2] 0 0
MTD and RP2D of Ixabepilone When Administered With Lapatinib Plus Capecitabine
Timepoint [2] 0 0
Days 1 through 21
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Baseline to Day 21, continuously
Secondary outcome [2] 0 0
Number of Participants With DLT
Timepoint [2] 0 0
Baseline to Day 21, continuously
Secondary outcome [3] 0 0
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Timepoint [3] 0 0
Baseline and weekly from Days 1 to 21 (Cycle 1)
Secondary outcome [4] 0 0
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Timepoint [4] 0 0
At baseline and within 72 hours of Day 1 of 21-day cycle
Secondary outcome [5] 0 0
Maximum Concentration of Ixabepilone
Timepoint [5] 0 0
Day 1 of 21-day cycle
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Day 1 of 21-day cycle
Secondary outcome [7] 0 0
Terminal Half-life of Ixabepilone
Timepoint [7] 0 0
Day 1 of 21-day cycle
Secondary outcome [8] 0 0
Time to Peak Concentration of Ixabepilone
Timepoint [8] 0 0
Day 1 of 21-day cycle
Secondary outcome [9] 0 0
Volume of Distribution at Steady State of Ixabepilone
Timepoint [9] 0 0
Day 1 of 21-day cycle
Secondary outcome [10] 0 0
Overall Tumor Response By Number of Participants
Timepoint [10] 0 0
Baseline and Day 21 (21-day cycle)
Secondary outcome [11] 0 0
Duration of Response of Combination Treatment With Ixabepilone Plus Lapatinib
Timepoint [11] 0 0
First occurrence of PR or CR to PD or Death (no average, as no data available)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2010
Sample size
Target
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Local Institution - Brisbane
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Italy
State/province [2] 0 0
Modena

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
R-Pharm
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00634088