NSABP B-47 - Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer
Description
A Randomized Phase III Trial of Adjuvant Therapy Comparing Chemotherapy Alone (Six Cycles of TC or Four Cycles of AC Followed by Four Cycles of Weekly Paclitaxel) to Chemotherapy Plus Trastuzumab in Women with Node-Positive or High-Risk Node-Negative HER2-Normal Invasive Breast Cancer
Primary:
To determine whether the addition of trastuzumab to chemotherapy (TC or AC?WP) improves invasive disease-free survival (IDFS) in women with resected node-positive or high-risk node-negative breast cancer which is reported as HER2-low by all HER2 testing performed
Study/Treatment
Breast Cancer
Inclusion/Notes
Eligibility Criteria:
Age > 18 years.
Pre- or postmenopausal
ECOG performance status of 0 or 1
ANC must be = 1,200/mm3
Platelet count must be = 100,000/mm3
Hemoglobin must be = 10 g/dL
Total bilirubin must be = ULN for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert disease or similar syndrome involving slow conjugation of bilirubin
Alkaline phosphatase must be = 2.5 x ULN for the lab
AST must be = 1.5 x ULN for the lab (if ALT is performed instead of AST [per institution's standard practice], the ALT value must be = 1.5 x ULN; if both were performed, the AST must be = 1.5 x ULN)
Alkaline phosphatase and AST may not both be > the ULN
Patients with AST or alkaline phosphatase > 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
Patients with alkaline phosphatase that is > ULN but = 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease
The most recent postoperative serum creatinine performed within 6 weeks prior to randomization must be = ULN for the lab
Not pregnant or nursing
Negative pregnancy test
LVEF assessment must be performed within 90 days prior to randomization;
LVEF assessment performed by 2-D echocardiogram is preferred, however, MUGA scan may be substituted based on institutional preferences
For patients who will receive the TC chemotherapy regimen, the LVEF must be = 50% regardless of the cardiac-imaging facility's lower limit of normal
For patients who will receive the AC?WP chemotherapy regimen, the LVEF must be = 55% regardless of the cardiac-imaging facility's lower limit of normal
[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 > 70%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain.]
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
No cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens, including, but not limited to:
Active cardiac disease:
Angina pectoris that requires the current use of anti-anginal medication
Ventricular arrhythmias except for benign premature ventricular contractions
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
Conduction abnormality requiring a pacemaker
Valvular disease with documented compromise in cardiac function
Symptomatic pericarditis
History of cardiac disease:
Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function
History of documented CHF
Documented cardiomyopathy
No hypertension defined according to the following ineligibility criteria:
For patients who will receive TC (regardless of the patient's age): uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
For patients < 50 years old who will receive AC?WP: uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
For patients = 50 years old who will receive AC?WP: uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg OR controlled hypertension (systolic BP = 150 mm Hg and = 90 mmHg), if anti-hypertensive medication(s) are needed
[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.]
No active hepatitis B or hepatitis C with abnormal liver function tests
No intrinsic lung disease resulting in dyspnea
No poorly controlled diabetes mellitus
No active infection or chronic infection requiring chronic suppressive antibiotics
No nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) = grade 2, per the CTCAE v4.0
No conditions that would prohibit administration of corticosteroids
No known hypersensitivity to any of the study drugs or excipients, e.g., polysorbate 80 and Cremophor® EL
No other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
Principal Name
Mark A. Taylor, MD
Phone
(912) 819-5704
Nancy N. and J.C. Lewis Cancer & Research Pavilion225 Candler Drive, Savannah, Georgia 31405
