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Carboplatin and Paclitaxel With or Without Panitumumab in Treating Patients With Invasive Triple Negative Breast Cancer

Primary Purpose

Breast Carcinoma, Breast Lump, Edema

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Laboratory Biomarker Analysis
Paclitaxel
Panitumumab
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histological confirmation of breast carcinoma
  • Patients must have invasive breast cancer (IBC), confirmed according to international consensus criteria:

    • Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass
    • Duration: History of such findings no more than 6 months
    • Extent: Erythema occupying at least 1/3 of whole breast
    • Pathology: Pathologic confirmation of invasive carcinoma
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10%
  • Patients have left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9.0 g/dL
  • Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) =< 3.0 x ULN
  • Alkaline phosphatase (ALP) =< 2.5 x ULN
  • Total bilirubin =< 1.5 x ULN
  • Creatinine (Cr) =< 1.5 mg/dL x ULN
  • Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockroft-Gault
  • Patients have the ability and willingness to sign written informed consent
  • Patients of childbearing potential (women who are postmenopausal for < 1 year, not surgically sterilized, or not abstinent), have a negative urine pregnancy test, and agree to the consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile before the female subject's entry into the study and is the sole sexual partner for that female subject; intrauterine device, oral contraception, or barrier methods, including diaphragm or condom with a spermicide

Exclusion Criteria:

  • Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e. radiation and/or surgery), and are not candidates for breast surgery will not be eligible
  • History of radiotherapy for current breast cancer diagnosis
  • History of recent malignancies < 5 years (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ)
  • Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection
  • History of extensive interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of extensive interstitial lung disease on baseline chest computed tomography (CT) scan
  • Other known other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with a peripheral neuropathy > grade 1
  • Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration
  • Patients have a history of prior therapy with carboplatin
  • Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2
  • Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph nodes
  • Patients have history of diagnosed interstitial lung disease

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A (panitumumab, paclitaxel, carboplatin)

Group B (paclitaxel, carboplatin)

Arm Description

Patients receive panitumumab IV over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.

Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.

Outcomes

Primary Outcome Measures

Complete pathologic response
Will be estimated for each treatment arm with exact 95% confidence intervals. A Chi-square test or Fisher's exact test will be used to compare the differences in complete pathologic response rate between the two treatment arms. A logistic regression model will be used to assess the differences in complete pathologic response between the two treatment arms, adjusting for other covariates as appropriate. The analysis will be based on the modified intent-to-treat population.

Secondary Outcome Measures

Disease free survival
The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes.
Overall survival
The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes.
Incidence of adverse events
Descriptive statistics will be used.

Full Information

First Posted
August 18, 2016
Last Updated
September 19, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02876107
Brief Title
Carboplatin and Paclitaxel With or Without Panitumumab in Treating Patients With Invasive Triple Negative Breast Cancer
Official Title
A Randomized Phase II Study of Neoadjuvant Carboplatin/Paclitaxel (CT) Versus Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen for Newly Diagnosed Primary Triple-Negative Inflammatory Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 6, 2016 (Actual)
Primary Completion Date
October 31, 2025 (Anticipated)
Study Completion Date
October 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This randomized phase II trial studies how well carboplatin and paclitaxel with or without panitumumab work in treating patients with invasive triple negative breast cancer. Drugs used in the chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping the them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Giving carboplatin and paclitaxel with or without panitumumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the pathologic complete response (pCR) rate in patients with primary triple-receptor negative (estrogen receptor [ER]-negative, progesterone receptor [PgR]-negative, and human epidermal growth factor receptor 2 [HER2]-negative) inflammatory breast cancer (TN-IBC) by using a combination of panitumumab, carboplatin, and paclitaxel (PaCT) in comparison with carboplatin and paclitaxel (CT) followed by adriamycin and cyclophosphamide (AC) in a neoadjuvant setting. SECONDARY OBJECTIVES: I. To determine the disease-free survival (DFS) rates produced by either arm of trial combination treatment. II. To determine the overall survival (OS) rates produced by either arm of trial combination treatment. III. To determine the safety and tolerability of both arms of trial combination treatment. EXPLORATORY OBJECTIVES: I. To determine whether the pCR rate positively correlates with reduced nodal expression status. II. To determine whether the pCR rate inversely correlates with arginine methylation status of epidermal growth factor receptor (EGFR). III. To identify molecular biomarkers predictive of the pCR rate by analysis of multiplexed immunohistochemical (IHC) staining. IV. To identify molecular biomarkers predictive of the pCR rate by genomic and proteomic analysis. V. To determine whether the inhibition of the EGFR pathway downregulates the COX-2 pathway and mesenchymal marker. OUTLINE: Patients are randomized into 1 of 2 groups. GROUP A: Patients receive panitumumab intravenously (IV) over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. GROUP B: Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are followed up at 1 month and then annually for at least 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Carcinoma, Breast Lump, Edema, Erythema, Estrogen Receptor Negative, HER2/Neu Negative, Inflammatory Breast Carcinoma, Invasive Breast Carcinoma, Peau d'Orange, Progesterone Receptor Negative, Triple-Negative Breast Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A (panitumumab, paclitaxel, carboplatin)
Arm Type
Experimental
Arm Description
Patients receive panitumumab IV over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.
Arm Title
Group B (paclitaxel, carboplatin)
Arm Type
Experimental
Arm Description
Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, Vectibix
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Complete pathologic response
Description
Will be estimated for each treatment arm with exact 95% confidence intervals. A Chi-square test or Fisher's exact test will be used to compare the differences in complete pathologic response rate between the two treatment arms. A logistic regression model will be used to assess the differences in complete pathologic response between the two treatment arms, adjusting for other covariates as appropriate. The analysis will be based on the modified intent-to-treat population.
Time Frame
At the time of surgery, assessed up to 5 years
Secondary Outcome Measure Information:
Title
Disease free survival
Description
The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes.
Time Frame
Up to 5 years
Title
Overall survival
Description
The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes.
Time Frame
Up to 5 years
Title
Incidence of adverse events
Description
Descriptive statistics will be used.
Time Frame
Up to 5 years
Other Pre-specified Outcome Measures:
Title
Reduced nodal expression status
Description
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used.
Time Frame
Up to 5 years
Title
Arginine methylation status of EGFR
Description
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used.
Time Frame
Up to 5 years
Title
Molecular biomarkers assessed by genomic and proteomic analysis
Description
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used.
Time Frame
Up to 5 years
Title
Downregulation of COX-2 pathway and mesenchymal marker by EGFR pathway
Description
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histological confirmation of breast carcinoma Patients must have invasive breast cancer (IBC), confirmed according to international consensus criteria: Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass Duration: History of such findings no more than 6 months Extent: Erythema occupying at least 1/3 of whole breast Pathology: Pathologic confirmation of invasive carcinoma Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10% Patients have left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization Absolute neutrophil count (ANC) >= 1.5 x 10^9/L Platelet count >= 100 x 10^9/L Hemoglobin >= 9.0 g/dL Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN) Alanine aminotransferase (ALT) =< 3.0 x ULN Alkaline phosphatase (ALP) =< 2.5 x ULN Total bilirubin =< 1.5 x ULN Creatinine (Cr) =< 1.5 mg/dL x ULN Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockroft-Gault Patients have the ability and willingness to sign written informed consent Patients of childbearing potential (women who are postmenopausal for < 1 year, not surgically sterilized, or not abstinent), have a negative urine pregnancy test, and agree to the consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile before the female subject's entry into the study and is the sole sexual partner for that female subject; intrauterine device, oral contraception, or barrier methods, including diaphragm or condom with a spermicide Exclusion Criteria: Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e. radiation and/or surgery), and are not candidates for breast surgery will not be eligible History of radiotherapy for current breast cancer diagnosis History of recent malignancies < 5 years (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ) Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection History of extensive interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of extensive interstitial lung disease on baseline chest computed tomography (CT) scan Other known other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients with a peripheral neuropathy > grade 1 Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration Patients have a history of prior therapy with carboplatin Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2 Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph nodes Patients have history of diagnosed interstitial lung disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Azadeh Nasrazadani
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

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Carboplatin and Paclitaxel With or Without Panitumumab in Treating Patients With Invasive Triple Negative Breast Cancer

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