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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02876107
Recruitment Status : Recruiting
First Posted : August 23, 2016
Last Update Posted : October 1, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Drug: Carboplatin Other: Laboratory Biomarker Analysis Drug: Paclitaxel Biological: Panitumumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 6, 2016
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : October 31, 2024


Arm Intervention/treatment
Experimental: Group A (panitumumab, paclitaxel, carboplatin)
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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Panitumumab
Given IV
Other Names:
  • ABX-EGF
  • ABX-EGF Monoclonal Antibody
  • ABX-EGF, Clone E7.6.3
  • MoAb ABX-EGF
  • Monoclonal Antibody ABX-EGF
  • Vectibix

Experimental: Group B (paclitaxel, carboplatin)
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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat




Primary Outcome Measures :
  1. Complete pathologic response [ Time Frame: At the time of surgery, assessed up to 5 years ]
    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 :
  1. Disease free survival [ Time Frame: Up to 5 years ]
    The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes.

  2. Overall survival [ Time Frame: Up to 5 years ]
    The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes.

  3. Incidence of adverse events [ Time Frame: Up to 5 years ]
    Descriptive statistics will be used.


Other Outcome Measures:
  1. Reduced nodal expression status [ Time Frame: Up to 5 years ]
    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.

  2. Arginine methylation status of EGFR [ Time Frame: Up to 5 years ]
    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.

  3. Molecular biomarkers assessed by genomic and proteomic analysis [ Time Frame: Up to 5 years ]
    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.

  4. Downregulation of COX-2 pathway and mesenchymal marker by EGFR pathway [ Time Frame: Up to 5 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02876107


Contacts
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Contact: Naoto Ueno, MD, PHD 713-792-2817 nueno@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Naoto T. Ueno    713-792-2817      
Principal Investigator: Naoto T. Ueno         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Naoto Ueno M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02876107    
Other Study ID Numbers: 2016-0177
NCI-2017-00619 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0177 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 23, 2016    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Inflammatory Breast Neoplasms
Erythema
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Skin Manifestations
Signs and Symptoms
Paclitaxel
Carboplatin
Albumin-Bound Paclitaxel
Panitumumab
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs