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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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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.