Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer

<p>Inclusion Criteria:</p><ul><li>The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination</li><li><p>All of the following staging criteria (according to the 7th edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual) must be met:</p><ul><li>By pathologic evaluation, primary tumor must be pT1-3</li><li><p>By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b,pN1c), pN2a, pN2b, pN3a, or pN3b</p><ul><li><p>If pN0, one of the following criteria must be met:</p><ul><li>pT2 and estrogen receptor (ER) negative and progesterone receptor (PgR) negative</li><li>pT2 and ER positive (PgR status may be positive or negative) and either grade 3histology or Oncotype DX Recurrence Score of &gt;= 25; or</li><li>pT3 regardless of hormone receptor status, histologic grade, and Oncotype DX Recurrence Score</li></ul></li></ul></li></ul></li><li>No T4 tumors including inflammatory breast cancer</li><li><p>No definitive clinical or radiologic evidence of metastatic disease</p><ul><li>NOTE: Chest imaging (mandatory for all patients) and other imaging (if required) must have been performed within 90 days prior to randomization</li></ul></li><li>No synchronous or previous contralateral invasive breast cancer (patients with synchronous and&#x2F;or previous contralateral DCIS or lobular carcinoma in situ [LCIS] are eligible)</li><li>No previous ipsilateral invasive breast cancer or ipsilateral DCIS (patients with synchronous or previous ipsilateral LCIS are eligible)</li><li><p>HER2 status of the primary tumor must be evaluated prior to randomization; all testing performed must indicate that the tumor is HER2-low as defined below</p><ul><li>IHC must be performed and the IHC staining results must indicate a score of 1+ (in situ hybridization [ISH] testing is not required) or 2+ (ISH must also be performed and must indicate that the tumor is HER2-low as described below)</li><li>If ISH testing is performed, test results must be as follows and IHC must be 1+ or 2+: The ratio of HER2 to CEP17 must be &lt; 2.0 or, if a ratio was not performed, the HER2 gene copy number must be &lt; 4 per nucleus</li><li>Note: If the IHC staining intensity is reported as a range, e.g., 0 to 1+ or 1+ to 2+, the higher intensity score in the range should be used to determine eligibility</li></ul></li><li><p>No primary tumor with any of the following HER2 testing results:</p><ul><li><p>IHC staining intensity:</p><ul><li>0 on all evaluations of specimens</li><li>3+ on evaluation of any specimen</li></ul></li><li>ISH with a ratio of HER2 to CEP17 &gt;= 2.0 on evaluation of any specimen</li><li>ISH result indicating HER2 gene copy number &gt;= 4 per nucleus on evaluation of any specimen</li></ul></li><li><p>The patient must have undergone either a total mastectomy or breast-conserving surgery (lumpectomy) (patients who have had a nipple-sparing mastectomy are eligible)</p><ul><li>For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist; if pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible (patients with margins positive for LCIS are eligible without additional resection)</li><li>For patients who undergo mastectomy, margins must be free of gross residual tumor(patients with microscopic positive margins are eligible as long as post-mastectomy RT of the chest wall will be administered)</li><li>The interval between the last surgery for breast cancer (treatment or staging) and randomization must be no more than 84 days</li></ul></li><li><p>The patient must have completed one of the procedures for evaluation of pathologic nodal status listed below:</p><ul><li><p>Sentinel lymphadenectomy alone:</p><ul><li>If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or pN1b</li><li>If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1a, the primary tumor must be T1 or T2 by pathologic evaluation and the nodal involvement must be limited to 1 or 2 positive nodes</li></ul></li><li>Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive</li><li>Axillary lymphadenectomy with or without SN isolation procedures</li></ul></li><li>The patient must have ER analysis performed on the primary tumor prior to randomization; if ER analysis is negative, then PgR analysis must also be performed (either the core biopsy or surgical resection specimen can be used for ER&#x2F;PgR testing); patients with a primary tumor that is hormone receptor-positive or receptor-negative are eligible</li><li>Pre- or postmenopausal</li><li>Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1</li><li>Absolute neutrophil count (ANC) must be &gt;= 1,200&#x2F;mm^3</li><li>Platelet count must be &gt;= 100,000&#x2F;mm^3</li><li>Hemoglobin must be &gt;= 10 g&#x2F;dL</li><li>Total bilirubin must be =&lt; upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation &gt; ULN to 1.5 x ULN due to Gilbert disease or similar syndrome involving slow conjugation of bilirubin</li><li>Alkaline phosphatase must be =&lt; 2.5 x ULN for the lab</li><li>Aspartate aminotransferase (AST) must be =&lt; 1.5 x ULN for the lab (if alanine aminotransferase [ALT] is performed instead of AST [per institution&#x27;s standard practice], the ALT value must be =&lt; 1.5 x ULN; if both were performed, the AST must be =&lt; 1.5 x ULN)</li><li>Alkaline phosphatase and AST may not both be &gt; the ULN</li><li>Patients with AST or alkaline phosphatase &gt; ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the above requirements are met</li><li>Patients with alkaline phosphatase that is &gt; ULN but =&lt; 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, positron emission tomography (PET)-computed tomography (CT) scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease</li><li>The most recent post operative serum creatinine performed within 6 weeks prior to randomization must be =&lt; ULN for the lab</li><li>Not pregnant or nursing</li><li>Negative pregnancy test</li><li><p>Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days prior to randomization; LVEF assessment performed by 2-dimensional (D) echo cardiogram is preferred, however, multi-gated acquisition (MUGA) scan maybe substituted based on institutional preferences</p><ul><li>For patients who will receive the TC chemotherapy regimen, the LVEF must be &gt;= 50% regardless of the cardiac-imaging facility&#x27;s lower limit of normal</li><li>For patients who will receive the AC→WP chemotherapy regimen, the LVEF must be &gt;= 55% regardless of the cardiac-imaging facility&#x27;s lower limit of normal</li><li>NOTE: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments, it is critical that this baseline study be an accurate assessment.
If the baseline LVEF is &gt; 70%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain</li></ul></li><li>No history of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization</li><li><p>No cardiac disease (history of and&#x2F;or active disease) that would preclude the use of the drugs included in the treatment regimens, including, but not limited to:</p><ul><li><p>Active cardiac disease:</p><ul><li>Angina pectoris that requires the current use of anti-anginal medication</li><li>Ventricular arrhythmias except for benign premature ventricular contractions</li><li>Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication</li><li>Conduction abnormality requiring a pacemaker</li><li>Valvular disease with documented compromise in cardiac function</li><li>Symptomatic pericarditis</li></ul></li><li><p>History of cardiac disease:</p><ul><li>Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricle (LV) function</li><li>History of documented congestive heart failure (CHF)</li><li>Documented cardiomyopathy</li></ul></li></ul></li><li><p>No hypertension defined according to the following ineligibility criteria:</p><ul><li>For patients who will receive TC (regardless of the patient&#x27;s age): uncontrolled hypertension defined as sustained systolic blood pressure (BP) &gt; 150 mm Hg or diastolic BP &gt; 90 mm Hg (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)</li><li>For patients &lt; 50 years old who will receive AC→WP: uncontrolled hypertension defined as sustained systolic BP &gt; 150 mm Hg or diastolic BP &gt; 90 mm Hg (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)</li><li>For patients &gt;= 50 years old who will receive AC→WP: uncontrolled hypertension defined as sustained systolic BP &gt; 150 mm Hg or diastolic BP &gt; 90 mm Hg OR controlled hypertension (systolic BP =&lt; 150 mm Hg and diastolic BP =&lt; 90 mmHg), if anti-hypertensive medication(s) are needed</li><li>NOTE: Patients who are not eligible based on the AC→WP regimen BP criteria but who meet the TC regimen BP criteria are eligible for B-47 if the intended chemotherapy regimen is changed to TC</li></ul></li><li>No active hepatitis B or hepatitis C with abnormal liver function tests</li><li>No intrinsic lung disease resulting in dyspnea</li><li>No poorly controlled diabetes mellitus</li><li>No active infection or chronic infection requiring chronic suppressive antibiotics</li><li>No nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) &gt;= grade 2, per the Common Terminology Criteria for Adverse Events (CTCAE) v4.0</li><li>No conditions that would prohibit administration of corticosteroids</li><li>No known hypersensitivity to any of the study drugs or excipients, e.g., polysorbate 80 and Cremophor EL</li><li>No other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up</li><li>No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements</li><li>Concurrent participation in NSABP-B-39 allowed</li><li>No previous therapy with anthracyclines, taxanes, or trastuzumab for any malignancy</li><li>No chemotherapy or HER2-targeted therapy administered for the currently diagnosed breast cancer prior to randomization</li><li>No whole-breast radiation therapy (RT) prior to randomization or partial-breast RT that cannot be completed on or before the date of randomization</li><li>No use of any investigational product within 30 days prior to randomization</li><li>No continued endocrine therapy such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor (patients are eligible if these medications are discontinued prior to randomization)</li><li>No continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy (patients are eligible if these medications are discontinued prior to randomization)</li><li>No chronic daily treatment with corticosteroids with a dose of &gt;= 10 mg&#x2F;day methylprednisol one equivalent (excluding inhaled steroids)</li><li>No other concurrent chemotherapy</li><li>No other concurrent targeted therapy for malignancy</li><li>No partial-breast irradiation following randomization</li></ul>

<p>Inclusion Criteria:</p><ul><li>Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer; (comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer)</li><li>Women of reproductive potential must agree to use an effective non-hormonal method of contraception (for example condoms, some intrauterine devices, diaphragms, tubal ligation, vasectomized partner, or abstinence) during therapy and for at least 6 months after the last dose of study therapy (chemotherapy or trastuzumab)</li><li>Submission of tumor samples from the breast surgery is required for all patients</li><li>The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines</li><li>Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1</li><li>The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination</li><li><p>All of the following staging criteria (according to the 7th edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual) must be met:</p><ul><li>By pathologic evaluation, primary tumor must be pT1-3</li><li><p>By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b,pN1c), pN2a, pN2b, pN3a, or pN3b</p><ul><li><p>If pN0, one of the following criteria must be met:</p><ul><li>pT2 and estrogen receptor (ER) negative and progesterone receptor (PgR) negative</li><li>pT2 and ER positive (PgR status may be positive or negative) and either grade 3histology or Oncotype DX Recurrence Score of &gt;= 25; or</li><li>pT3 regardless of hormone receptor status, histologic grade, and Oncotype DX Recurrence Score</li></ul></li></ul></li></ul></li><li><p>HER2 status of the primary tumor must be evaluated prior to randomization; all testing performed must indicate that the tumor is HER2-low as defined below</p><ul><li>IHC must be performed and the IHC staining results must indicate a score of 1+ (in situ hybridization [ISH] testing is not required) or 2+ (ISH must also be performed and must indicate that the tumor is HER2-low as described below)</li><li>If ISH testing is performed, test results must be as follows and IHC must be 1+ or 2+: The ratio of HER2 to CEP17 must be &lt; 2.0 or, if a ratio was not performed, the HER2 gene copy number must be &lt; 4 per nucleus</li><li>Note: If the IHC staining intensity is reported as a range, e.g., 0 to 1+ or 1+ to 2+, the higher intensity score in the range should be used to determine eligibility</li></ul></li><li><p>The patient must have undergone either a total mastectomy or breast-conserving surgery (lumpectomy) (patients who have had a nipple-sparing mastectomy are eligible)</p><ul><li>For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist; if pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible (patients with margins positive for LCIS are eligible without additional resection)</li><li>For patients who undergo mastectomy, margins must be free of gross residual tumor(patients with microscopic positive margins are eligible as long as post-mastectomy RT of the chest wall will be administered)</li><li>The interval between the last surgery for breast cancer (treatment or staging) and randomization must be no more than 84 days</li></ul></li><li>For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist; if pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection)</li><li>For patients who undergo mastectomy, margins must be free of gross residual tumor; (patients with microscopic positive margins are eligible as long as post-mastectomy radiation therapy [RT] of the chest wall will be administered)</li><li><p>The patient must have completed one of the procedures for evaluation of pathologic nodal status listed below:</p><ul><li><p>Sentinel lymphadenectomy alone:</p><ul><li>If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or pN1b</li><li>If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1a, the primary tumor must be T1 or T2 by pathologic evaluation and the nodal involvement must be limited to 1 or 2 positive nodes</li></ul></li><li>Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive</li><li>Axillary lymphadenectomy with or without SN isolation procedures</li></ul></li><li>The interval between the last surgery for breast cancer (treatment or staging) and randomization must be no more than 84 days</li><li>The patient must have ER analysis performed on the primary tumor prior to randomization; if ER analysis is negative, then PgR analysis must also be performed (either the core biopsy or surgical resection specimen can be used for ER&#x2F;PgR testing); patients with a primary tumor that is hormone receptor-positive or receptor-negative are eligible</li><li>Absolute neutrophil count (ANC) must be &gt;= 1,200&#x2F;mm^3</li><li>Platelet count must be &gt;= 100,000&#x2F;mm^3</li><li>Hemoglobin must be &gt;= 10 g&#x2F;dL</li><li>Total bilirubin must be =&lt; upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation &gt; ULN to 1.5 x ULN due to Gilbert disease or similar syndrome involving slow conjugation of bilirubin</li><li>Alkaline phosphatase must be =&lt; 2.5 x ULN for the lab</li><li>Aspartate aminotransferase (AST) must be =&lt; 1.5 x ULN for the lab (if alanine aminotransferase [ALT] is performed instead of AST [per institution&#x27;s standard practice], the ALT value must be =&lt; 1.5 x ULN; if both were performed, the AST must be =&lt; 1.5 x ULN)</li><li>Patients with alkaline phosphatase that is &gt; ULN but =&lt; 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, positron emission tomography (PET)-computed tomography (CT) scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease</li><li>Patients with AST or alkaline phosphatase &gt; ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the above requirements are met</li><li>Alkaline phosphatase and AST may not both be &gt; the ULN</li><li>The most recent post operative serum creatinine performed within 6 weeks prior to randomization must be =&lt; ULN for the lab</li><li><p>Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days prior to randomization; LVEF assessment performed by 2-dimensional (D) echo cardiogram is preferred, however, multi-gated acquisition (MUGA) scan maybe substituted based on institutional preferences</p><ul><li>For patients who will receive the TC chemotherapy regimen, the LVEF must be &gt;= 50% regardless of the cardiac-imaging facility&#x27;s lower limit of normal</li><li>For patients who will receive the AC-WP chemotherapy regimen, the LVEF must be &gt;= 55% regardless of the cardiac-imaging facility&#x27;s lower limit of normal</li><li>NOTE: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments, it is critical that this baseline study be an accurate assessment.
If the baseline LVEF is &gt; 70%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain</li></ul></li></ul><p>Exclusion Criteria:</p><ul><li><p>Primary tumor with any of the following human epidermal growth factor receptor (HER2) testing results:</p><ul><li><p>Immunohistochemistry (IHC) staining intensity:</p><ul><li>0 on all evaluations of specimens</li><li>3+ on evaluation of any specimen</li></ul></li><li>In situ hybridization (ISH) with a ratio of HER2 to chromosome enumeration probe 17 (CEP17) &gt;= 2.0 on evaluation of any specimen</li><li>ISH result indicating HER2 gene copy number &gt;= 4 per nucleus on evaluation of any specimen</li></ul></li><li>T4 tumors including inflammatory breast cancer</li><li><p>Definitive clinical or radiologic evidence of metastatic disease</p><ul><li>NOTE: Chest imaging (mandatory for all patients) and other imaging (if required) must have been performed within 90 days prior to randomization</li></ul></li><li>Synchronous or previous contralateral invasive breast cancer (patients with synchronous and&#x2F;or previous contralateral DCIS or lobular carcinoma in situ [LCIS] are eligible)</li><li>Previous ipsilateral invasive breast cancer or ipsilateral DCIS (patients with synchronous or previous ipsilateral LCIS are eligible)</li><li>History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization</li><li>Previous therapy with anthracyclines, taxanes, or trastuzumab for any malignancy</li><li>Chemotherapy or HER2-targeted therapy administered for the currently diagnosed breast cancer prior to randomization</li><li>Whole-breast radiation therapy (RT) prior to randomization or partial-breast RT that cannot be completed on or before the date of randomization</li><li>Continued endocrine therapy such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor (patients are eligible if these medications are discontinued prior to randomization)</li><li>Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy (patients are eligible if these medications are discontinued prior to randomization)</li><li><p>Cardiac disease (history of and&#x2F;or active disease) that would preclude the use of the drugs included in the treatment regimens, including, but not confined to:</p><ul><li><p>Active cardiac disease:</p><ul><li>Angina pectoris that requires the current use of anti-anginal medication</li><li>Ventricular arrhythmias except for benign premature ventricular contractions</li><li>Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication</li><li>Conduction abnormality requiring a pacemaker</li><li>Valvular disease with documented compromise in cardiac function</li><li>Symptomatic pericarditis</li></ul></li><li><p>History of cardiac disease:</p><ul><li>Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricle (LV) function</li><li>History of documented congestive heart failure (CHF)</li><li>Documented cardiomyopathy</li></ul></li></ul></li><li><p>Hypertension defined according to the following ineligibility criteria:</p><ul><li>For patients who will receive TC (regardless of the patient&#x27;s age): uncontrolled hypertension defined as sustained systolic blood pressure (BP) &gt; 150 mm Hg or diastolic BP &gt; 90 mm Hg (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)</li><li>For patients &lt; 50 years old who will receive AC-WP: uncontrolled hypertension defined as sustained systolic BP &gt; 150 mm Hg or diastolic BP &gt; 90 mm Hg; patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria</li><li>For patients &gt;= 50 years old who will receive AC-WP: uncontrolled hypertension defined as sustained systolic BP &gt; 150 mm Hg or diastolic BP &gt; 90 mm Hg</li><li>Controlled hypertension (systolic BP =&lt; 150 mm Hg and diastolic BP =&lt; 90 mmHg), if anti-hypertensive medication(s) are needed</li><li>NOTE: Patients who are not eligible based on the AC-WP regimen BP criteria but who meet the TC regimen BP criteria are eligible for B-47 if the intended chemotherapy regimen is changed to TC</li></ul></li><li>Active hepatitis B or hepatitis C with abnormal liver function tests</li><li>Intrinsic lung disease resulting in dyspnea</li><li>Poorly controlled diabetes mellitus</li><li>Active infection or chronic infection requiring chronic suppressive antibiotics</li><li>Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) &gt;= grade 2, per the Common Terminology Criteria for Adverse Events (CTCAE) v4.0</li><li>Conditions that would prohibit administration of corticosteroids</li><li>Chronic daily treatment with corticosteroids with a dose of &gt;= 10 mg&#x2F;day methylprednisol one equivalent (excluding inhaled steroids)</li><li>Known hypersensitivity to any of the study drugs or excipients, e.g., polysorbate 80 and Cremophor EL</li><li>Pregnancy or lactation at the time of study entry; (Note: pregnancy testing must be performed within 2 weeks prior to randomization according to institutional standards for women of childbearing potential)</li><li>Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up</li><li>Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements</li><li>Use of any investigational product within 30 days prior to randomization</li></ul>

Fcγ receptor polymorphism

Fcgamma receptor polymorphism

The polymorphism of the Fcγ 158 receptor gene will be dichotomized as V/V (valine) vs. other genotypes and the polymorphism of the Fcγ 131 receptor gene will be dichotomized as H/H (histidine) vs. other genotypes to evaluate an interaction between treatment group and Fcγ polymorphism.
The Kaplan-Meier method105 will be used to estimate the distribution of the primary endpoints stratified by the dichotomized subgroups, and the log-rank test106 will be used to statistically compare the time-to-event distributions.

The polymorphism of the Fcgamma 158 receptor gene will be dichotomized as V/V (valine) vs. other genotypes and the polymorphism of the Fcgamma 131 receptor gene will be dichotomized as H/H (histidine) vs. other genotypes to evaluate an interaction between treatment group and Fcgamma polymorphism.
The Kaplan-Meier method105 will be used to estimate the distribution of the primary endpoints stratified by the dichotomized subgroups, and the log-rank test106 will be used to statistically compare the time-to-event distributions.

ACTIVE_NOT_RECRUITING

TERMINATED

RECRUITING

ACTIVE_NOT_RECRUITING

Tania E. Cortas

Christopher T. Stokoe

602-277-4868

888-823-5923

Tania E. Cortas

Christopher T. Stokoe

ACTIVE_NOT_RECRUITING

RECRUITING

NEA Baptist Clinic-Matthews

Fowler Family Center for Cancer Care

RECRUITING

TERMINATED

Providence Saint Joseph Medical Center

Providence Saint Joseph Medical Center/Disney Family Cancer Center

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

TERMINATED

RECRUITING

TERMINATED

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

TERMINATED

Bay Area Tumor Institute

Bay Area Tumor Institute CCOP

RECRUITING

TERMINATED

Saint Joseph Hospital

Saint Joseph Hospital - Orange

412-330-4624

888-823-5923

Mary.ketner@nsabp.org

ctsucontact@westat.com

RECRUITING

ACTIVE_NOT_RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

RECRUITING

TERMINATED

RECRUITING

TERMINATED

RECRUITING

TERMINATED

RECRUITING

ACTIVE_NOT_RECRUITING

Memorial Hospital Colorado Springs

Rocky Mountain Cancer Centers-Penrose

80909

80907

Dax Kurbegov

Keren Sturtz

719-365-2406

888-785-6789

Dax Kurbegov

Keren Sturtz

Saint Anthony Central Hospital

Memorial Hospital Colorado Springs

Denver

Colorado Springs

80204

80909

Keren Sturtz

Wendy S. Oatis

888-785-6789

719-365-2406

Keren Sturtz

Wendy S. Oatis

39.73915

38.83388

-104.9847

-104.82136

Swedish Medical Center

Colorado Blood Cancer Institute

Englewood

Denver

80110

80907

39.64777

39.73915

-104.98776

-104.9847

Poudre Valley Hospital

Mercy Medical Center

Fort Collins

Durango

80524

81301

Paolo Romero

Keren Sturtz

970-495-8226

888-785-6789

Paolo Romero

Keren Sturtz

40.58526

37.27528

-105.08442

-107.88007

Front Range Cancer Specialists

Comprehensive Cancer Care and Research Institute of Colorado LLC

Fort Collins

Englewood

80528

80113

Diana C. Medgyesy

Keren Sturtz

970-212-7600

888-785-6789

Diana C. Medgyesy

Keren Sturtz

40.58526

39.64777

-105.08442

-104.98776

Saint Mary's Hospital and Regional Medical Center

Swedish Medical Center

ACTIVE_NOT_RECRUITING

RECRUITING

Grand Junction

Englewood

81502

80113

39.06387

39.64777

-108.55065

-104.98776

North Suburban Medical Center

Rocky Mountain Cancer Centers - Pueblo

ACTIVE_NOT_RECRUITING

RECRUITING

Thornton

Pueblo

80229

81008

39.86804

38.25445

-104.97192

-104.60914

RECRUITING

ACTIVE_NOT_RECRUITING

06520-8032

06520

Anca M. Bulgaru

Dennis E. Slater

Anca M. Bulgaru

Dennis E. Slater

RECRUITING

ACTIVE_NOT_RECRUITING

John L. Zapas

Claudine Isaacs

443-777-7364

202-444-0381

John L. Zapas

Claudine Isaacs

RECRUITING

WITHDRAWN

University of Florida

Broward Health Medical Center

ACTIVE_NOT_RECRUITING

RECRUITING

Gainesville

Fort Lauderdale

32610

33316

29.65163

26.12231

-82.32483

-80.14338

Craig H. Reynolds

Christopher T. Stokoe

412-330-4624

888-823-5923

Mary.ketner@nsabp.org

ctsucontact@westat.com

Craig H. Reynolds

Christopher T. Stokoe

M D Anderson Cancer Center- Orlando

UF Cancer Center at Orlando Health

Northeast Georgia Cancer Care LLC

University Cancer and Blood Center LLC

RECRUITING

ACTIVE_NOT_RECRUITING

Emory University

Emory University/Winship Cancer Institute

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

Thomas E. Seay

Andrew W. Pippas

678-843-7119

706-660-6404

Thomas E. Seay

Andrew W. Pippas

RECRUITING

TERMINATED

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

Kapiolani Medical Center at Pali Momi

Pali Momi Medical Center

ACTIVE_NOT_RECRUITING

TERMINATED

RECRUITING

ACTIVE_NOT_RECRUITING

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

ACTIVE_NOT_RECRUITING

TERMINATED

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

ACTIVE_NOT_RECRUITING

TERMINATED

RECRUITING

ACTIVE_NOT_RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

Sherman Hospital

Advocate Sherman Hospital

Cancer Institute at Alexian Brothers

Alexian Brothers Medical and Cancer Center

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

ACTIVE_NOT_RECRUITING

RECRUITING

Medical and Surgical Specialists

Illinois CancerCare-Galesburg Cottage Plaza Office

Delnor Community Hospital

Western Illinois Cancer Treatment Center

Geneva

Galesburg

60134

61401

Perry J. Menini

Nguyet A. Le-Lindqwister

630-208-4563

800-793-2262

Perry J. Menini

Nguyet A. Le-Lindqwister

41.88753

40.94782

-88.30535

-90.37124

ACTIVE_NOT_RECRUITING

TERMINATED

ACTIVE_NOT_RECRUITING

TERMINATED

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

ACTIVE_NOT_RECRUITING

TERMINATED

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

Good Samaritan Regional Medical Center

Good Samaritan Regional Health Center

ACTIVE_NOT_RECRUITING

TERMINATED

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

ACTIVE_NOT_RECRUITING

TERMINATED

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

Advocate Lutheran General Hospital

Radiation Oncology of Northern Illinois

Park Ridge

Ottawa

60068

61350

Jacob D. Bitran

Nguyet A. Le-Lindqwister

847-384-3621

800-793-2262

Jacob D. Bitran

Nguyet A. Le-Lindqwister

42.01114

41.34559

-87.84062

-88.84258

Pekin Cancer Treatment Center

Advocate Lutheran General Hospital.

Pekin

Park Ridge

61554

60068

John W. Kugler

Jacob D. Bitran

800-793-2262

847-384-3621

John W. Kugler

Jacob D. Bitran

40.56754

42.01114

-89.64066

-87.84062

Illinois CancerCare-Pekin

Pekin Cancer Treatment Center

61603

61554

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

Methodist Medical Center of Illinois

Illinois CancerCare-Pekin

Peoria

Pekin

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

40.69365

40.56754

-89.58899

-89.64066

Proctor Hospital

Methodist Medical Center of Illinois

61614

61603

Illinois CancerCare-Peoria

Proctor Hospital

RECRUITING

TERMINATED

61615

61614

Illinois Oncology Research Association CCOP

OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC

61615

61615-7827

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

OSF Saint Francis Medical Center

Illinois CancerCare-Peoria

61637

61615

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

Illinois CancerCare-Peru

Illinois Oncology Research Association CCOP

Peru

Peoria

61354

61615

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

41.32753

40.69365

-89.12897

-89.58899

Illinois Valley Hospital

OSF Saint Francis Medical Center

ACTIVE_NOT_RECRUITING

RECRUITING

Peru

Peoria

61354

61637

41.32753

40.69365

-89.12897

-89.58899

Illinois CancerCare-Princeton

Illinois CancerCare-Peru

Princeton

Peru

61356

61354

John W. Kugler

Nguyet A. Le-Lindqwister

John W. Kugler

Nguyet A. Le-Lindqwister

41.36809

41.32753

-89.46481

-89.12897

Perry Memorial Hospital

Illinois Valley Hospital

ACTIVE_NOT_RECRUITING

TERMINATED

Princeton

Peru

61356

61354

41.36809

41.32753

-89.46481

-89.12897

West Suburban Cancer Center

Valley Radiation Oncology

River Forest

Peru

60305

61354

Isoken Koko

Nguyet A. Le-Lindqwister

708-488-0882

800-793-2262

Isoken Koko

Nguyet A. Le-Lindqwister

41.89781

41.32753

-87.81395

-89.12897

Swedish American Hospital

Illinois CancerCare-Princeton

TERMINATED

RECRUITING

Rockford

Princeton

61104

61356

42.27113

41.36809

-89.094

-89.46481

Saint Anthony Medical Center

Perry Memorial Hospital

Rockford

Princeton

61108

61356

42.27113

41.36809

-89.094

-89.46481

Illinois CancerCare-Spring Valley

West Suburban Medical Center

ACTIVE_NOT_RECRUITING

RECRUITING

Spring Valley

River Forest

61362

60305

41.32754

41.89781

-89.19981

-87.81395

Carle Foundation - Carle Cancer Center

Carle Cancer Center

Central DuPage Hospital Cancer Center

Cadence Cancer Center in Warrenville

Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

Fort Wayne Medical Oncology and Hematology Inc-Parkview

800-777-7775

317-621-7104

Franciscan St. Francis Health

Franciscan Saint Francis Health-Indianapolis

800-777-7775

317-621-7104

Saint Anthony Memorial Health Center

Franciscan Saint Anthony Health-Michigan City

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

TERMINATED

708-915-6747

708-915-4673

McFarland Clinic

McFarland Clinic PC-William R Bliss Cancer Center

Helen G Nassif Community Cancer Center

Physicians' Clinic of Iowa PC

David W. Zenk

Willilam P. Fusselman

David W. Zenk

Willilam P. Fusselman

David W. Zenk

Willilam P. Fusselman

David W. Zenk

Willilam P. Fusselman

ACTIVE_NOT_RECRUITING

RECRUITING

David W. Zenk

Willilam P. Fusselman

David W. Zenk

Willilam P. Fusselman

ACTIVE_NOT_RECRUITING

RECRUITING

Medical Oncology and Hematology Associates

Medical Oncology and Hematology Associates-Laurel

Owensboro Mercy Medical Center

Merle Mahr Cancer Center

Owensboro

Madisonville

42303

42431

James R. Thomas

Peter S. Tate

270-688-3691

859-260-6425

James R. Thomas

Peter S. Tate

37.77422

37.3281

-87.11333

-87.49889

504-568-3410

504-568-2428

aconne1@lsuhsc.edu

emede1@lsuhsc.edu

Ochsner Clinic Foundation-Baton Rouge

Ochsner Health Center-Summa

Ochsner North Shore Medical Center

Ochsner Health Center-Covington

504-568-3410

504-568-2428

aconne1@lsuhsc.edu

emede1@lsuhsc.edu

504-568-3410

504-568-2428

aconne1@lsuhsc.edu

emede1@lsuhsc.edu

RECRUITING

WITHDRAWN

Ochsner Clinic Foundation

Ochsner Medical Center Jefferson

Louisiana State University

Louisiana State University Health Sciences Center Shreveport

University of Maryland Greenebaum Cancer Center

University of Maryland/Greenebaum Cancer Center

21201-1595

21201

Veterans Administration Medical Center

Veterans Administration Medical Center-Baltimore

John L. Zapas

Claudine Isaacs

443-777-7364

202-444-0381

John L. Zapas

Claudine Isaacs

John L. Zapas

Claudine Isaacs

443-777-7364

202-444-0381

John L. Zapas

Claudine Isaacs

RECRUITING

ACTIVE_NOT_RECRUITING

Johns Hopkins University

Johns Hopkins University/Sidney Kimmel Cancer Center

21287-8936

21287

21014

21015

RECRUITING

ACTIVE_NOT_RECRUITING

412-330-4624

888-823-5923

Mary.ketner@nsabp.org

ctsucontact@westat.com

Western Maryland Health System

Western Maryland Regional Medical Center

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

TERMINATED

RECRUITING

ACTIVE_NOT_RECRUITING

Washington County Hospital

Meritus Medical Center

21740

21742

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

978-283-4000

978-283-4000ext559

RECRUITING

ACTIVE_NOT_RECRUITING

Addison Gilbert Hospital

MetroWest Medical Center-Framingham Union Hospital

RECRUITING

TERMINATED

Gloucester

Framingham

01930

01702

42.61405

42.27926

-70.66313

-71.41617

RECRUITING

TERMINATED

ACTIVE_NOT_RECRUITING

RECRUITING

Bay Regional Medical Center

McLaren-Bay Region

Mecosta County Medical Center

Spectrum Health Big Rapids Hospital

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

TERMINATED

McLaren Regional Medical Center

McLaren-Flint

ACTIVE_NOT_RECRUITING

TERMINATED

Saint Mary's Health Care

Mercy Health Saint Mary's

Ingham Regional Medical Center

McLaren-Greater Lansing

Deimante M. Tamkus

Justin F. Klamerus

517-334-2765

800-248-6777

Deimante M. Tamkus

Justin F. Klamerus

Mount Clemens Regional Medical Center

McLaren-Macomb

Mercy Health Partners-Mercy Campus

Mercy Health Mercy Campus

William Beaumont Hospital

William Beaumont Hospital-Royal Oak

Mayo Clinic Health System in Mankato

Mayo Clinic Health Systems-Mankato

56002

56001

CentraCare Clinic

Coborn Cancer Center at Saint Cloud Hospital

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

504-568-3410

504-568-2428

aconne1@lsuhsc.edu

emede1@lsuhsc.edu

504-568-3410

504-568-2428

aconne1@lsuhsc.edu

emede1@lsuhsc.edu

65203

65212

Carl G. Kardinal

Akm Mosharraf Hossain

Carl G. Kardinal

Akm Mosharraf Hossain

RECRUITING

ACTIVE_NOT_RECRUITING

Saint John's Regional Medical Center

Mercy Hospital-Joplin

RECRUITING

ACTIVE_NOT_RECRUITING

ACTIVE_NOT_RECRUITING

TERMINATED

TERMINATED

WITHDRAWN

Liberty Radiation Oncology Clinic

Liberty Hospital

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

Saint John's Hospital

Mercy Hospital Springfield

Cox Medical Center

CoxHealth South Hospital

RECRUITING

ACTIVE_NOT_RECRUITING

ACTIVE_NOT_RECRUITING

TERMINATED

ACTIVE_NOT_RECRUITING

TERMINATED

ACTIVE_NOT_RECRUITING

WITHDRAWN

ACTIVE_NOT_RECRUITING

TERMINATED

ACTIVE_NOT_RECRUITING

TERMINATED

ACTIVE_NOT_RECRUITING

TERMINATED

ACTIVE_NOT_RECRUITING

TERMINATED

Lincoln Medical Education Foundation Cancer Resource Center

Nebraska Cancer Research Center

James A. Reilly

Robert M. Langdon

James A. Reilly

Robert M. Langdon

702-731-8274

702-384-0013

702-731-8274

702-384-0013

Steven S. Larmon

Mary D. Chamberlin

603-354-5454

800-639-6918

jmichelson@cheshire-med.com

cancer.research.nurse@dartmouth.edu

Steven S. Larmon

Mary D. Chamberlin

603-354-5454

603-354-5454ext2155

RECRUITING

ACTIVE_NOT_RECRUITING

RECRUITING

ACTIVE_NOT_RECRUITING

Margarette R. Bryan

Robert Wieder

Margarette R. Bryan

Robert Wieder

South Jersey Healthcare

Inspira Medical Center Vineland

RECRUITING

TERMINATED

518-489-3612

518-489-3612ext1342

518-489-3612

518-489-3612ext1342

RECRUITING

TERMINATED

607-547-6965

607-547-3073

jennifer.victory@bassett.org

diana.crean@bassett.org

Hematology Oncology Associates of Central New York PC

Hematology Oncology Associates of Central New York PC-East Syracuse

518-489-3612

518-489-3612ext1342

Monter Cancer Center

New York Oncology Hematology PC - Latham

RECRUITING

TERMINATED

Lake Success

Latham

11042

12110

40.77066