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)
Overview
- Phase
- Phase 2
- Intervention
- Doxorubicin
- Conditions
- HER2-negative Breast Cancer
- Sponsor
- NSABP Foundation Inc
- Enrollment
- 64
- Locations
- 43
- Primary Endpoint
- Pathologic complete response (PCR) to study therapy (both breast and lymph node-combined; ypT0/Tis ypN0)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Nodal status - negative: Imaging of the axilla is negative; Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node(s) on imaging is negative;
- •Nodal status - positive: FNA or core biopsy of the node(s) is cytologically or histologically suspicious or positive. Imaging is suspicious or abnormal but FNA or core biopsy was not performed.
- •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:
Exclusion Criteria
- •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.
Arms & Interventions
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
Intervention: Doxorubicin
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
Intervention: Cyclophosphamide
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
Intervention: Weekly Paclitaxel
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
Intervention: Trastuzumab
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
Intervention: Pertuzumab
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
Intervention: Celcuity CELx HSF
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Pathologic complete response to study therapy (breast)(From initiation of study therapy to time of surgery, which is usually performed 3 to 4 weeks after completion of study therapy)
- Clinical complete response (both breast and axilla)(From initiation of study therapy to 2-4 weeks after completion of study therapy)
- Residual cancer burden (RCB)(From initiation of study therapy to time of surgery, which is usually performed 3 to 4 weeks after completion of study therapy)
- Logistic regression(From prior to study entry (time of CELx score assay) to 4-6 weeks after surgery (pCR outcome determination))
- Frequency of adverse events assessed by CTCAE 4.0(From beginning of study therapy to 4-6 weeks after surgery)