Study of Neoadjuvant Chemotherapy Plus Trastuzumab and Pertuzumab in HER2-Negative Breast Cancer Patients With Abnormal HER2 Signaling (FB-12)
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|ClinicalTrials.gov Identifier: NCT03412643|
Recruitment Status : Recruiting
First Posted : January 26, 2018
Last Update Posted : April 7, 2020
|First Submitted Date ICMJE||January 12, 2018|
|First Posted Date ICMJE||January 26, 2018|
|Last Update Posted Date||April 7, 2020|
|Actual Study Start Date ICMJE||May 14, 2018|
|Estimated Primary Completion Date||October 30, 2020 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Pathologic complete response (PCR) to study therapy (both breast and lymph node-combined; ypT0/Tis ypN0) [ Time Frame: From initiation of study therapy to time of surgery, which is usually performed 3 to 4 weeks after completion of study therapy ]
Percentage of patients with absence of residual invasive cancer in H&E slides of resected breast specimens and all sampled regional lymph nodes following the completion of neoadjuvant systemic therapy
|Original Primary Outcome Measures ICMJE||Not Provided|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Study of Neoadjuvant Chemotherapy Plus Trastuzumab and Pertuzumab in HER2-Negative Breast Cancer Patients With Abnormal HER2 Signaling|
|Official Title ICMJE||An Open-Label Phase II Trial to Evaluate the Efficacy and Safety of Neoadjuvant Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel Plus Trastuzumab and Pertuzumab in Early Stage HER2-Negative Breast Cancer Patients Selected With a Test Measuring Live Cell HER2 Signaling Transduction (FACT 1)|
|Brief Summary||This is a prospective, single arm, open label, multicenter interventional study designed to evaluate the efficacy of neoadjuvant chemotherapy with anti-HER2 antibodies in patients with HER2-negative invasive breast cancer who have abnormal HER2 signaling activity determined by the Celcuity CELx HER2 Signaling Function (HSF) testing.|
Patients will be required to have a prescreening research core needle biopsy to procure a fresh tumor specimen that will be sent to Celcuity for CELx HSF testing, in order to assess the status of their HER2 signaling activity (abnormally or normally active).
Patients who have abnormal HER2 signaling activity will receive weekly paclitaxel plus the anti-HER2 therapy regimen of trastuzumab and pertuzumab following completion of initial doxorubicin/cyclophosphamide.The primary endpoint of the study is to evaluate whether patients with HER2-negative breast cancers based on standard American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) testing criteria, but with abnormal HER2-driven signaling pathways determined by the Celcuity HSF assay and receive HER2-targeted therapy with neoadjuvant chemotherapy, will have a higher rate of pathological complete response in the breast and lymph nodes (pCR breast and lymph nodes) than has been found historically in patients with HER2-negative breast cancer who have received neoadjuvant chemotherapy alone. Secondary endpoints include pathologic complete response (breast), clinical complete response (cCR), residual cancer burden (RCB) 0-1 index, and relationship between quantitative CELx score and pCR rate.
It is expected that approximately 270 patients will need to be prescreened in order to enroll 54 patients (26 ER-positive/HER2-negative and 28 ER-negative/HER2-negative) who have abnormal HER2 signaling activity.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||HER2-negative Breast Cancer|
|Study Arms ICMJE||Experimental: Arm 1
Celcuity CELx HSF Test on tumor material obtained from research core biopsy to select patients with abnormal HER2 signaling tumors
Doxorubicin + cyclophosphamide followed by Weekly Paclitaxel +Trastuzumab+Pertuzumab
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Not Provided|
|Estimated Study Completion Date ICMJE||March 30, 2021|
|Estimated Primary Completion Date||October 30, 2020 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
SCREENING PRIOR TO INITIATING CHEMOTHERAPY
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
The primary breast tumor must be palpable and measure greater than or equal 2.0 cm on physical exam.
The regional lymph nodes can be cN0, cN1, or cN2a.
Histological grade II or III tumor.
Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound, and/or MRI) within 6 weeks prior to initiating chemotherapy. If suspicious or abnormal, FNA or core biopsy is recommended, also within 6 weeks prior to initiating chemotherapy. Findings of these evaluations will be used to determine the nodal status prior to initiating chemotherapy.
Tumor specimen obtained at the time of diagnosis must have ER and progesterone receptor (PgR) analysis assessed by current ASCO/CAP Guidelines. Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.
Tumor specimen obtained at the time of diagnosis must have been determined to be HER2-negative as follows:
Blood counts performed within 6 weeks prior to initiating chemotherapy must meet the following criteria:
The following criteria for evidence of adequate hepatic function performed within 6 weeks prior to initiating chemotherapy must be met:
Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 6 weeks prior to initiating chemotherapy does not demonstrate metastatic disease and the requirements in next criteria are met.
Patients with alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or positron emission tomography (PET) scan performed within 6 weeks prior to initiating chemotherapy does not demonstrate metastatic disease.
Serum creatinine performed within 6 weeks prior to initiating chemotherapy must be less than or equal to 1.5 x ULN for the lab.
The left ventricular ejection fraction (LVEF) assessment by echocardiogram or multi-gated acquisition (MUGA) scan performed within 90 days prior to initiating chemotherapy must be greater than or equal 55 percent regardless of the facility's lower limit of normal (LLN).
Patients with reproductive potential must agree to use an effective non-hormonal method of contraception during therapy and for at least 7 months after the last dose of study
MAIN STUDY ENROLLMENT
Tumor determined to have abnormal HER2-driven signaling activity based on the CELx HSF test.
T4 tumors including inflammatory breast cancer.
FNA alone to diagnose the breast cancer.
Excisional biopsy or lumpectomy performed prior to initiating chemotherapy.
Surgical axillary staging procedure prior to initiating chemotherapy. Pre-neoadjuvant therapy sentinel node biopsy is not permitted. (FNA or core biopsy is acceptable.)
Definitive clinical or radiologic evidence of metastatic disease. Required imaging studies must have been performed within 6 weeks prior to initiating chemotherapy.
Synchronous bilateral invasive breast cancer. (Patients with synchronous and/or previous contralateral ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS] are eligible.)
Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
Previous therapy with anthracycline, taxanes, trastuzumab, or other HER2 targeted therapies for any malignancy.
Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to initiating chemotherapy.)
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 2 years prior to initiating chemotherapy.
Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to:
Uncontrolled hypertension defined as sustained systolic BP greater than 150 mmHg or diastolic BP greater than 90 mmHg. (Patients with initial BP elevations are eligible prior to initiating chemotherapy if initiation or adjustment of BP medication lowers pressure.)
Active hepatitis B or hepatitis C with abnormal liver function tests. Intrinsic lung disease resulting in dyspnea.
Poorly controlled diabetes mellitus.
Active infection or chronic infection requiring chronic suppressive antibiotics.
Patients known to be HIV positive.
Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) greater than or equal to grade 2, per the CTCAE v4.0.
Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function.
Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up.
Conditions that would prohibit administration of corticosteroids.
Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
Known hypersensitivity to any of the study drugs or any of the ingredients or excipients of these drugs (e.g., Cremophor EL), including sensitivity to benzyl alcohol.
Pregnancy or lactation at the initiation of chemotherapy. (Note: Pregnancy testing must be performed within 2 weeks prior to initiating chemotherapy according to institutional standards for women of childbearing potential.)
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03412643|
|Other Study ID Numbers ICMJE||NSABP FB-12|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||NSABP Foundation Inc|
|Study Sponsor ICMJE||NSABP Foundation Inc|
|PRS Account||NSABP Foundation Inc|
|Verification Date||March 2020|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP