A Phase II Combination of Trastuzumab and Ixabepilone Versus Trastuzumab and Docetaxel in Patients With Advanced and/or Metastatic Breast Cancer

NCT00490646 | Completed Phase 2 Results

• 2 other identifiers: CA163-140Eudract No: 2007-000721-21
• Study Type: interventional
• Target: 50
• Locations: 5 countries
• Sites: 19

Brief Summary

The purpose of this randomized, Phase 2 open-label study was to assess the response rate of participants with Human Epidermal Growth Factor Receptor 2 (Her2+) locally advanced and/or metastatic breast cancer (not previously treated with chemotherapy or trastuzumab) to treatment with ixabepilone plus trastuzumab and/or docetaxel plus trastuzumab.

Conditions

Metastatic Breast Cancer

Keywords

Locally advanced and/or metastatic breast cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1)

  Percentage of participants with best overall response (BOR) of either complete response (CR) or partial response (PR) according to RECIST version 1.1 as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A two-sided confidence interval (CI) was computed using the Clopper-Pearson method.

  Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)

• Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  BOR was the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. Refer to Outcome Measure 3 for definition of PD.

  Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).

• Time to Response

  From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)

• Duration of Response

  From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)

• Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0

  Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)

• Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0

  Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)

Study Arms (2)

Arm A

EXPERIMENTAL

trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.

Drug: ixabepilone; Drug: trastuzumab

Arm B

ACTIVE COMPARATOR

trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.

Drug: docetaxel; Drug: trastuzumab

Interventions

ixabepilone DRUG

Ixabepilone 40 mg/m\^2 was administered as a 3-hour I.V. continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity. For the first cycle, ixabepilone was administered the day following the first dose of trastuzumab (in the first cycle trastuzumab was given on Day 0); in all the following cycles, ixabepilone was administered immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Also known as: BMS-247550, Epothilone, IXEMPRA®

Arm A

docetaxel DRUG

Docetaxel 100 mg/m\^2 was administered as a 1-hour IV continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity. For the first cycle, docetaxel was administered the day following the first dose of trastuzumab (i.e. in the first cycle trastuzumab was given on Day 0); in all following cycles, docetaxel was administered immediately after trastuzumab if the preceding dose of trastuzumab was well tolerated.

Arm B

trastuzumab DRUG

Trastuzumab was administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle at a dose of 2 mg/kg until disease progression or unacceptable toxicity. In cycle 1, a loading dose of 4 mg/kg was administered as a 90-minute IV infusion on a day before initial administration of chemotherapy (i.e. on Day 0). Trastuzumab was given immediately prior to ixabepilone (Arm A) or docetaxel (Arm B) in all subsequent cycles as a 30-minute IV infusion if the initial dose was well tolerated.

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally advanced or metastatic HER2+ breast cancer not previously treated with chemotherapy or trastuzumab.
• Subjects who had received prior (neo)adjuvant chemotherapy or trastuzumab were eligible except if they relapsed within 12 months after the last dose of a taxane or trastuzumab given as (neo)adjuvant therapy.
• Measurable disease
• Left Ventricular Ejection Fraction (LVEF) ≥50%

You may not qualify if:

• Prior chemotherapy or trastuzumab for metastatic breast cancer (MBC)
• Relapse within 1 year after (neo)adjuvant taxane or trastuzumab
• Neuropathy \> Grade 1
• Significant cardiovascular disease
• Any brain metastases

Sponsors & Collaborators

• R-Pharm: lead

Study Sites (19)

Local Institution

Caen, F-14076, France

Location

Local Institution

Grenoble, 38028, France

Location

Local Institution

Saint-Priest-en-Jarez, 42271, France

Location

Local Institution

Toulouse, 31300, France

Location

Local Institution

Athens, 11522, Greece

Location

Local Institution

Athens, 12462, Greece

Location

Local Institution

Pireaus, 18537, Greece

Location

Local Institution

Bologna, 40138, Italy

Location

Local Institution

Brescia, 25123, Italy

Location

Local Institution

Modena, 41100, Italy

Location

Local Institution

Napoli, 80131, Italy

Location

Local Institution

Roma, 00144, Italy

Location

Local Institution

Sora, 03039, Italy

Location

Local Institution

Madrid, 28007, Spain

Location

Local Institution

Madrid, 28034, Spain

Location

Local Institution

Ankara, 06100, Turkey (Türkiye)

Location

Local Institution

Ankara, 06500, Turkey (Türkiye)

Location

Local Institution

Izmir, 35100, Turkey (Türkiye)

Location

Local Institution

Izmir, 35340, Turkey (Türkiye)

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ixabepilone; Epothilones; Docetaxel; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2007
• First Posted: June 25, 2007
• Study Start: February 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: November 1, 2011
• Last Updated: March 10, 2016
• Results First Posted: July 18, 2012

Record last verified: 2016-02

Locations

ES (2); FR (4); GR (3); TU (4); IT (6)