Randomized Phase II Study of Ixabepilone Alone and Ixabepilone Plus Cetuximab as First-Line Treatment for Female Subjects With Triple Negative Locally Advanced Non-resectable and/or Metastatic Breast Cancer

NCT00633464 | Completed Phase 2 Results

• 1 other identifier: CA163-139
• Study Type: interventional
• Target: 79
• Locations: 7 countries
• Sites: 19

Brief Summary

The purpose of this study was to estimate the response rate of ixabepilone monotherapy, and the combination of ixabepilone plus cetuximab as first-line treatment of female subjects with triple negative (estrogen receptor \[ER\], progesterone receptor \[PR\], Human Epidermal Growth Factor Receptor 2 \[HER2\] negative) locally advanced non-resectable and/or metastatic breast cancer

Conditions

Triple Negative Locally Advanced Non-resectable Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST])

  The participant had an OR if her best overall response (BOR) during the study was either a complete response (CR) or a partial response (PR) according to the RECIST 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 target lesions. Confidence interval (CI) was Computed using Clopper-Pearson method.

  Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until disease progression (maximum participant objective response of 18.3 weeks)

• Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST)

  PD = At least a 20% increase in the sum of LD of target lesions in reference to the smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. 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 target lesions.

  Assessed at 6 week intervals for first 12 months from randomization, thereafter every 3 months (to a maximum follow-up for tumor response of 17 months).

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 17 months)

• Time to Response

  Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until CR or PR (maximum participant time to response of 18.3 weeks.)

• Duration of Response

  From the date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 15.6 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. Median time on ixapebilone therapy was 15 weeks (range: 3-54 weeks for ixabepilone arm; 3-36 weeks for ixabepilone+cetuximab arm)

• Number of Participants With Hematology Abnormalities

  Assessed prior to 1st cycle, at beginning of each cycle, weekly (cetuximab treatment), and every 4 weeks within 30 days after last dose of study drug. Median time on ixapebilone therapy: 15 weeks (range:3-54:ixabepilone arm;3-36:ixapebilone+cetuximab arm)

Study Arms (2)

Arm A (ixabepilone 40 mg^2)

EXPERIMENTAL

ixabepilone 40 mg/m\^2 every 3 weeks

Drug: ixabepilone

Arm B (cetuximab 250 mg/m^2 + ixabepilone 40 mg/m^2)

EXPERIMENTAL

cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks

Drug: ixabepilone + cetuximab

Interventions

ixabepilone DRUG

injection, intravenous (IV), until unacceptable toxicity or progression or 15 months after the Last Subject First Visit (LSFV), whichever comes first. Ixabepilone 40 mg/m\^2 was administered as a 3-hour IV continuous infusion on Day 1 in a 21-day cycle provided the participant met the re-treatment criteria.

Also known as: IXEMPRA, BMS-247550

Arm A (ixabepilone 40 mg^2)

ixabepilone + cetuximab DRUG

Ixabepilone: injection, IV, until unacceptable toxicity or progression or 15 months after the LSFV, whichever comes first. Ixabepilone 40 mg/m\^2 was administered as a 3-hour IV continuous infusion on Day 1 in a 21-day cycle provided the participant meets the re-treatment criteria. Cetuximab: injection, IV, until unacceptable toxicity or progression or 15 months after the LSFV, whichever comes first. Cetuximab 400 mg/m\^2 was administered as a 2-hour IV loading dose via in-line filtration with an infusion pump, gravity drip, or a syringe pump on Day 1 of first cycle then 250 mg/m\^2 1-hour IV once a week, i.e. on Days 1, 8, and 15 of each cycle provided the participant meets the re-treatment criteria.

Also known as: IXEMPRA, BMS-247550, ERBITUX, BMS-564717

Arm B (cetuximab 250 mg/m^2 + ixabepilone 40 mg/m^2)

Eligibility Criteria

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

You may qualify if:

• Female subjects with triple negative (ER, PR, and HER2 negative) locally advanced non-resectable and/or metastatic breast cancer
• Prior adjuvant or neoadjuvant anthracycline-based chemotherapy

You may not qualify if:

• Tumors that are fluorescence in situ hybridization test (FISH) positive or immunohistochemistry (IHC) 3+
• Neuropathy \> Grade 1
• Prior systemic therapy for metastatic disease

Sponsors & Collaborators

• R-Pharm: lead

Study Sites (19)

Local Institution

Graz, 8036, Austria

Location

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Vienna, 1090, Austria

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Brno, 656 53, Czechia

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Prague, 128 08, Czechia

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Prague, 150 06, Czechia

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Bayonne, 64100, France

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Dijon, 21079, France

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Lyon, 69008, France

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Paris, 75651, France

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Saint-Brieuc, 22015, France

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Saint-Herblain, 44805, France

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Toulouse, 31052, France

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Thessaloniki, 54642, Greece

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Napoli, 80131, Italy

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Gdansk, 80952, Poland

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Olsztyn, 10-513, Poland

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Barcelona, 08036, Spain

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Barcelona, 08208, Spain

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Barcelona, 08221, Spain

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ixabepilone; Cetuximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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: March 5, 2008
• First Posted: March 12, 2008
• Study Start: June 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: May 1, 2011
• Last Updated: March 10, 2016
• Results First Posted: April 24, 2012

Record last verified: 2016-02

Locations

GR (1); IT (1); FR (7); AU (2); PL (2); CZ (3); ES (3)