Randomized Study Evaluating Ixabepilone Plus Capecitabine or Docetaxel Plus Capecitabine in Metastatic Breast Cancer - Full Text View

Sponsor:	Bristol-Myers Squibb
Information provided by (Responsible Party):	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00546364

Purpose

The purpose of this study is to assess the effect of ixabepilone plus capecitabine or docetaxel plus capecitabine on shrinking or slowing the growth of metastatic breast cancer in women. The safety of this combination therapy will also be evaluated.

Condition	Intervention	Phase
Breast Neoplasms	Drug: Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 Drug: Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 Drug: Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	IXTEND: A Randomized Phase 2 Study to Evaluate the Combination of Ixabepilone Plus Capecitabine or Capecitabine Plus Docetaxel in the Treatment of Metastatic Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Docetaxel Capecitabine Ixabepilone

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Number of Participants With Best Tumor Response as Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline to 6 weeks (end of Cycle 2) ] [ Designated as safety issue: No ]
RECIST definitions: Complete reponse (CR)=disappearance of all nontarget lesions; partial response (PR)=at least 30% reduction in the sum of the longest diameter (LD) of all target lesions in reference to the baseline sum LD; stable disease (SD)=neither PR nor progressive disease (PD) criteria were met; PD=at least 20% increase in the sum of the LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline. Tumor status assessed by investigator.
Percentage of Participants With Best Response to Treatment of Complete or Partial [ Time Frame: Baseline to 6 weeks (end of Cycle 2) ] [ Designated as safety issue: No ]
The tumor response rate is defined as the number of participants with a best tumor response of CR or PR (as assessed by the investigator according to RECIST criteria), divided by the number of participants randomized in that arm.

Secondary Outcome Measures:

Percentage of Triple-negative (TN) Participants With Best Response to Treatment of Complete or Partial [ Time Frame: Baseline to 6 weeks (end of Cycle 2) ] [ Designated as safety issue: No ]
The tumor response rate is defined as the total number of participants whose best response is CR or PR, divided by the number of randomized participants. Participants not evaluable for response are considered to be nonresponders. TN participants are those with tumors that do not express estrogen or progesterone receptors and that do not over express human epidermal growth factor receptor 2 (HER2).
Percentage of Nontriple-negative (NTN) Participants With Best Response to Treatment of Complete or Partial Per Cohort [ Time Frame: Baseline to 6 weeks (end of Cycle 2) ] [ Designated as safety issue: No ]
The tumor response rate is defined as the total number of participants whose best response is CR or PR, divided by the number of randomized participants. Participants not evaluable for response are considered to be nonresponders. NTN participants are who are not TN participants (TN participants are those with tumors that do not express estrogen or progesterone receptors and that do not overexpress HER2) and who received ixabepilone plus capecitabine or docetaxel plus capecitabine.
Number of Participants With Death, Adverse Events (AEs), Drug-related AEs, Serious AEs (SAEs), Drug-related SAEs, AEs Leading to Discontinuation (AEDs), Drug-related AEDs, and Drug-related Peripheral Neuropathy [ Time Frame: Baseline to end of Cycle 1 (21 days), continuously ] [ Designated as safety issue: Yes ]
An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related or of unknown relationship to study treatment. Grade 3=Severe, Grade 4=Life-threatening.
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade [ Time Frame: Baseline in Cycle 1 (21 days) and then prior to start of each 21-day cycle ] [ Designated as safety issue: Yes ]
CTC Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2=Moderate; minimal, local or noninvasive intervention indicated. Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4=Life-threatening consequences; urgent intervention indicated.
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results [ Time Frame: Baseline in Cycle 1 (21 days) and then prior to start of each 21-day cycle ] [ Designated as safety issue: Yes ]
ULN=Upper limit of normal among all laboratory ranges. Alanine aminotransferase (ALT) Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Aspartate aminotransferase (AST) Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. Creatine Grade 1: >ULN to 1.5*ULN; Grade 2: 1.5 to 3.0*ULN; Grade 3: >3.0 to 6.0*ULN; Grade 4: >6.0*ULN.
Time to Progression [ Time Frame: Baseline to date progressive disease reported ] [ Designated as safety issue: No ]
Time to progression is defined as the time from date of randomization until the date that PD is first reported. Participants who die without a reported prior progression are considered to have progressed on the day of their death. Those who did not progress or die are censored at the day of their last tumor assessment.
Duration of Response [ Time Frame: Baseline (date of randomization) to date CR or PR criteria first met ] [ Designated as safety issue: Yes ]
Duration of overall response is computed for participants whose best response is either PR or CR and is measured from the time measurement criteria are first met for CR or PR (whichever status is recorded first) until the first date of documented PD or death. Participants who did not relapse or die are censored on the date of their last tumor assessment.
Median Number of Treatment Cycles [ Time Frame: Day 1 to end of Cycle 18, maximum (54 weeks) ] [ Designated as safety issue: No ]
The first dosing date is defined as the date of the first dose of chemotherapy or capecitabine, whichever was administered first. Cycles are defined as the time from Day 1 of the cycle until the day before the next cycle. The last cycle per participant is the 21-day period following Day 1 of that cycle.

Enrollment:	62
Study Start Date:	February 2008
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2	Drug: Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 Ixabepilone, 40 mg/m^2, administered as a 3-hour intravenous (IV) infusion on Day 1 of a 21-day cycle plus capecitabine, 1000 mg/m^2, self-administered on an outpatient basis twice daily by mouth on Days 1 through 14 (±2 days) of each 21-day cycle. Other Names: IXEMPRA® BMS-247550
Experimental: Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2	Drug: Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 Ixabepilone, 32 mg/m^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle plus capecitabine, 1000 mg/m^2, self-administered on an outpatient basis twice daily by mouth on Days 1 through 14 (±2 days) of each 21-day cycle.
Active Comparator: Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2	Drug: Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2 Docetaxel 75 mg/m^2 administered as a 1-hour IV infusion on Day 1 of a 21-day cycle plus capecitabine, 1000 mg/m^2, self-administered on an outpatient basis twice daily by mouth on Days 1 through 14 (±2 days) of each 21-day cycle.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Participants with metastatic breast cancer
Measurable disease
Up to 1 chemotherapy regimen is acceptable. Participants who have received paclitaxel in the neoadjuvant or adjuvant setting acceptable, only if the last dose of paclitaxel was received 12 months or less before the treatment. There is no timeframe for prior paclitaxel in the metastatic setting.
Human epidermal growth factor receptor 2-positive participants allowed if they have progressed after receiving treatment with trastuzumab or lapatinib
Eastern Cooperative Oncology Group Performance status of 0-1
Age younger than 18 years
Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of investigational products

Exclusion Criteria:

More than 1 chemotherapy regimen for the treatment of metastatic breast cancer
Prior treatment with any epothilone, capecitabine, or docetaxel
Prior radiation must not have included 30% or more of major bone marrow-containing areas (pelvis, lumbar spine). If prior radiation was less than 30%, a minimum interval of 2 weeks must be allowed between the last radiation treatment and administration of study medication. There must be at least 1 week between focal/palliative radiation and administration of study medication.
Any current or previous history of brain and/or leptomeningeal metastases
Neuropathy greater than Grade 2
Any concurrent malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix
Uncontrolled diabetes mellitus
Chronic hepatitis
HIV-positive status
Administration of trastuzumab, lapatinib, bevacizumab, or other systemic treatment for cancer must be discontinued 28 days prior to study medication. Hormonal anticancer agents must be discontinued at least 14 days prior to study medication. Hormonal replacement therapy is acceptable
Biphosphonates for palliation of bone metastases allowed if initiated at least 7 days before study entry

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00546364

Show 60 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00546364 History of Changes
Other Study ID Numbers:	CA163-131
Study First Received:	October 17, 2007
Results First Received:	May 6, 2011
Last Updated:	October 18, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Docetaxel
Capecitabine
Fluorouracil
Epothilones
Antineoplastic Agents
Therapeutic Uses

Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on February 09, 2012