ICE: Neo-Adjuvant Study in Triple Negative Breast Cancer Patients

Sponsor
The Methodist Hospital Research Institute (Other)
Overall Status
Completed
CT.gov ID
NCT01097642
Collaborator
Bristol-Myers Squibb (Industry)
40
1
2
133.7
0.3

Study Details

Study Description

Brief Summary

Ixabepilone and capecitabine combination has demonstrated to be an active regimen in patients with metastatic breast cancer after failing other treatments. Cetuximab is active against tumors expressing epidermal growth factor receptor w/demonstrated activity in head & neck and colorectal tumors and may be effective in some breast cancers known to express EGFR. Study seeks to evaluate Ixabepilone alone or in combination with cetuximab as a an antitumor therapy w/randomization stratified by stage (T1N1-3M0 or T2-4 N0-3M0).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Ixabepilone and capecitabine combination has demonstrated to be an active regimen in patients with metastatic breast cancer (MBC) after failing an anthracycline and a taxane regimen. Cetuximab is active in tumors that express epidermal growth factor receptor (EGFR) with demonstrated activity in head and neck and colorectal tumors. A proportion of breast cancers are known to express EGFR. Cetuximab's mechanism of action suggests the possibility of efficacy in breast cancer patients, and several studies show that it may be efficacious in Triple Negative Breast Cancer (TNBC). This study seeks to evaluate Ixabepilone alone or in combination with cetuximab as a possible way to increase antitumor activity. In this randomized open-label phase II trial, patients will be randomized equally between 1) Ixabepilone or 2) Ixabepilone plus Cetuximab. Randomization will be stratified by disease stage (T1N1-3M0 or T2-4 N0-3M0).

The study's primary objective is to determine the pathologic complete response rate (pCR) (breast and axilla) of Ixabepilone versus Ixabepilone when combined with cetuximab in patients with invasive breast adenocarcinoma T1N1-N3M0 or T2-4 N0-3M0 disease who are triple negative and who are candidates for preoperative chemotherapy. The secondary objectives are to evaluate overall objective response rate in both treatment groups and to assess safety and toxicity of each regimen. There are also tertiary, exploratory objectives that will hopefully allow for the correlation of biomarker expression and response to treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Open-Label Neo-Adjuvant Phase II Study Comparing Ixabepilone (I) Vs. Ixabepilone Plus Cetuximab (IC) in Triple Negative Breast Cancer Patients
Actual Study Start Date :
Oct 10, 2008
Actual Primary Completion Date :
Dec 1, 2019
Actual Study Completion Date :
Dec 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Ixabepilone

Brand name is Ixempra ®; it is an epothilone B analog used in combination with other chemotherapeutics against cancer.

Drug: Ixabepilone
Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
Other Names:
  • azaepothilone B
  • Experimental: Ixabepilone plus Cetuximab

    Cetuximab, brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor and monoclonal antibody used with Ixabepilone against cancer.

    Drug: Cetuximab
    Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes.
    Other Names:
  • Erbitux
  • Drug: Ixabepilone
    Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
    Other Names:
  • azaepothilone B
  • Outcome Measures

    Primary Outcome Measures

    1. Complete Response Rate [one year after treatment]

      The study's primary objective is to determine the pathologic complete response rate (pCR) (breast and axilla) of Ixabepilone versus Ixabepilone when combined with cetuximab in patients with invasive breast adenocarcinoma T1N1-N3M0 or T2-4 N0-3M0 disease who are triple negative and who are candidates for preoperative chemotherapy. The criteria used: "Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.

    Secondary Outcome Measures

    1. Recurrence Free Survival (RFS) [Median 3-year]

      The secondary objective is to evaluate the RFS in both treatment groups. The criteria used: "Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.

    2. Safety and Toxicity of Both Treatment Regimens: Number of Participants With Adverse Events [one year after last treatment dose]

      The number of participants with adverse events will be measured. Toxicity/safety will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.3.0). Baseline signs and symptoms will be recorded and followed throughout the trial. Toxicity assessments will be continuous during treatment and the year of follow-up, after which all study drug-related toxicities will be deemed resolved, stabilized, or irreversible. Vital signs will be performed at baseline and will be monitored pre-dose and during study drug administration for Cycles 1 - 4. Chemistry and hematology laboratory tests will be done at baseline and prior to each subsequent chemotherapy cycle.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with histologic confirmation of invasive breast carcinoma.

    • Patients must have intact primary tumor.

    • Patients greater than or equal to 18 years.

    • Patients should have T1N1-3M0 or T2-4 N0-3M0.

    • Patients with bilateral breast cancer are eligible.

    • Patients with second primary breast cancers are eligible.

    • Patients should have a Karnofsky performance scale of greater than or equal to 70%.

    • Patients must have clinically measurable disease to be treated in the neoadjuvant setting.

    • Patients should have adequate bone marrow function, as defined by peripheral granulocyte count of greater than or equal to 1500/mm3, and platelet count greater than or equal to 100000mm3.

    • Patients must have adequate liver function with a bilirubin within normal laboratory values. Alkaline phosphatase and transaminases (ALT and AST) may be up to 1.5 x upper limit of normal (ULN) of the institution.

    • Patients should have adequate renal function with creatinine levels within normal range.

    • Patients should have a normal left ventricular ejection fraction (LVEF) of greater than or equal to 50%.

    • Negative serum or urine pregnancy test for a woman of childbearing potential (WOCBP).

    • WOCBP must use a reliable and appropriate contraceptive method during the study and six months after chemotherapy is completed. WOCBP are women who are not menopausal for 12 months or had no previous surgical sterilization.

    • Patients must agree to have study biopsies.

    • Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.

    Exclusion Criteria:
    • Patients with a history of other invasive malignancies diagnosed and treated within the previous 5 years, except non-melanoma skin cancer and non-invasive cervical cancer.

    • Her2Neu, ER and PR positive patients should be excluded.

    • Patients with Inflammatory breast cancer (IBC) are excluded.

    • Patients with an organ allograft or other history of immune compromise.

    • Prior treatment with any investigational drug within the preceding 4 weeks.

    • Chronic treatment with systemic steroids or another immunosuppressive agent.

    • A Known history of HIV seropositivity.

    • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin defined as 1 mg a day).

    • Other concurrent and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration).

    • Patients with a pre-existing peripheral neuropathy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Methodist Hospital Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • The Methodist Hospital Research Institute
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Jenny Chang, MD, The Methodist Hospital Research Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Jenny C. Chang, MD, Principal Investigator, The Methodist Hospital Research Institute
    ClinicalTrials.gov Identifier:
    NCT01097642
    Other Study ID Numbers:
    • Pro00002243
    • 0908-0265
    First Posted:
    Apr 1, 2010
    Last Update Posted:
    Sep 22, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ixabepilone Ixabepilone Plus Cetuximab
    Arm/Group Description Brand name is Ixempra ®; it is an epothilone B analog used in combination with other chemotherapeutics against cancer. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles. Cetuximab, brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor and monoclonal antibody used with Ixabepilone against cancer. Cetuximab: Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
    Period Title: Overall Study
    STARTED 15 25
    COMPLETED 15 25
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Ixabepilone Ixabepilone Plus Cetuximab Total
    Arm/Group Description Brand name is Ixempra ®; it is an epothilone B analog used in combination with other chemotherapeutics against cancer. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles. Cetuximab, brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor and monoclonal antibody used with Ixabepilone against cancer. Cetuximab: Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles. Total of all reporting groups
    Overall Participants 15 25 40
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    51
    57
    55
    Sex: Female, Male (Count of Participants)
    Female
    15
    100%
    25
    100%
    40
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    7
    46.7%
    7
    28%
    14
    35%
    Not Hispanic or Latino
    8
    53.3%
    18
    72%
    26
    65%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    6.7%
    1
    4%
    2
    5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    4
    26.7%
    3
    12%
    7
    17.5%
    White
    10
    66.7%
    21
    84%
    31
    77.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    15
    100%
    25
    100%
    40
    100%
    Triple Negative Negative Breast Cancer (T1N1-N3M0 or T2-4 N0-3M0) (Count of Participants)
    Count of Participants [Participants]
    14
    93.3%
    24
    96%
    38
    95%

    Outcome Measures

    1. Primary Outcome
    Title Complete Response Rate
    Description The study's primary objective is to determine the pathologic complete response rate (pCR) (breast and axilla) of Ixabepilone versus Ixabepilone when combined with cetuximab in patients with invasive breast adenocarcinoma T1N1-N3M0 or T2-4 N0-3M0 disease who are triple negative and who are candidates for preoperative chemotherapy. The criteria used: "Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.
    Time Frame one year after treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ixabepilone Ixabepilone Plus Cetuximab
    Arm/Group Description Brand name is Ixempra ®; it is an epothilone B analog used in combination with other chemotherapeutics against cancer. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles. Cetuximab, brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor and monoclonal antibody used with Ixabepilone against cancer. Cetuximab: Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
    Measure Participants 15 25
    Count of Participants [Participants]
    2
    13.3%
    8
    32%
    2. Secondary Outcome
    Title Recurrence Free Survival (RFS)
    Description The secondary objective is to evaluate the RFS in both treatment groups. The criteria used: "Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.
    Time Frame Median 3-year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ixabepilone Ixabepilone Plus Cetuximab
    Arm/Group Description Brand name is Ixempra ®; it is an epothilone B analog used in combination with other chemotherapeutics against cancer. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles. Cetuximab, brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor and monoclonal antibody used with Ixabepilone against cancer. Cetuximab: Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
    Measure Participants 15 25
    Count of Participants [Participants]
    9
    60%
    17
    68%
    3. Secondary Outcome
    Title Safety and Toxicity of Both Treatment Regimens: Number of Participants With Adverse Events
    Description The number of participants with adverse events will be measured. Toxicity/safety will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.3.0). Baseline signs and symptoms will be recorded and followed throughout the trial. Toxicity assessments will be continuous during treatment and the year of follow-up, after which all study drug-related toxicities will be deemed resolved, stabilized, or irreversible. Vital signs will be performed at baseline and will be monitored pre-dose and during study drug administration for Cycles 1 - 4. Chemistry and hematology laboratory tests will be done at baseline and prior to each subsequent chemotherapy cycle.
    Time Frame one year after last treatment dose

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ixabepilone Ixabepilone Plus Cetuximab
    Arm/Group Description Brand name is Ixempra ®; it is an epothilone B analog used in combination with other chemotherapeutics against cancer. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles. Cetuximab, brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor and monoclonal antibody used with Ixabepilone against cancer. Cetuximab: Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
    Measure Participants 15 25
    Count of Participants [Participants]
    15
    100%
    25
    100%

    Adverse Events

    Time Frame Safety was assessed from time of informed consent signing through 30 days after last treatment dose (an average of 12 weeks).
    Adverse Event Reporting Description
    Arm/Group Title Ixabepilone Ixabepilone Plus Cetuximab
    Arm/Group Description Brand name is Ixempra ®; it is an epothilone B analog used in combination with other chemotherapeutics against cancer. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles. Cetuximab, brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor and monoclonal antibody used with Ixabepilone against cancer. Cetuximab: Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes. Ixabepilone: Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
    All Cause Mortality
    Ixabepilone Ixabepilone Plus Cetuximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/25 (0%)
    Serious Adverse Events
    Ixabepilone Ixabepilone Plus Cetuximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/15 (13.3%) 6/25 (24%)
    Blood and lymphatic system disorders
    Neutropenia 0/15 (0%) 2/25 (8%)
    Gastrointestinal disorders
    GI Events 0/15 (0%) 1/25 (4%)
    Nervous system disorders
    Peripheral neuropathy 2/15 (13.3%) 2/25 (8%)
    Skin and subcutaneous tissue disorders
    Rash 0/15 (0%) 1/25 (4%)
    Other (Not Including Serious) Adverse Events
    Ixabepilone Ixabepilone Plus Cetuximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/15 (100%) 25/25 (100%)
    Blood and lymphatic system disorders
    Anemia 11/15 (73.3%) 18/25 (72%)
    General disorders
    Fatigue 10/15 (66.7%) 21/25 (84%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Jenny Chang
    Organization The Methodist Hospital Research Institute
    Phone 713 441-0680
    Email jcchang@houstonmethodist.org
    Responsible Party:
    Jenny C. Chang, MD, Principal Investigator, The Methodist Hospital Research Institute
    ClinicalTrials.gov Identifier:
    NCT01097642
    Other Study ID Numbers:
    • Pro00002243
    • 0908-0265
    First Posted:
    Apr 1, 2010
    Last Update Posted:
    Sep 22, 2021
    Last Verified:
    Aug 1, 2021