Clinical trial NCT01501487: MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I
Official title: MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Breast Cancer
Keywords: breast cancer
neo adjuvant therapy
Lead sponsor: Agendia
Sponsor class: INDUSTRY
Collaborators: name: University of South Florida
name: University of Miami
name: Morton Plant Mease Health Care
name: AdventHealth
name: Plano Cancer Center
name: Ohio State University Comprehensive Cancer Center
name: University of Oklahoma
name: University of South Alabama
First posted: 2011-12-29
Enrollment: 226
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Genomics assays that measure specific gene expression patterns in a patient's primary tumor have become important prognostic tools for breast cancer patients. This study is designed to test the ability of MammaPrint® in combination with TargetPrint®, BluePrint®, and TheraPrint®, as well as traditional pathologic and clinical prognostic factors, to predict responsiveness to neo-adjuvant chemotherapy in patients with locally advanced breast cancer (LABC).

Detailed description: Patients with suspected primary breast cancer on mammography and clinical examination will be assessed for eligibility by having a needle core biopsy to confirm invasive carcinoma.

A fresh unfixed tumor specimen, incisional or core biopsy will be sent to Agendia to determine the MammaPrint risk profile, the BluePrint molecular subtyping profile, the TargetPrint ER, PR and HER2 single gene readout, the 56-geneTheraPrint Research Gene Panel and the additional genes as measured on the whole genome (44k) array.

Surgical Protocol:

1. Determination of nodal status:

   * For clinically node-negative patients: Axillary ultra sound, followed by Sentinel Lymph Node (SLN) biopsy
   * For clinically node-positive patients: ultra sound-guided Fine Needle Aspirate (FNA), followed by core biopsy
2. Neo-adjuvant chemotherapy
3. Definitive surgery:

   * For node-positive patients: lumpectomy, repeat SLN biopsy, Axillary Lymph Node Dissection (ALND)
   * For node-negative patients: lumpectomy, repeat SLN biopsy (optional), no ALND

Response will be measured by pathological Complete Response (pCR) and by centrally assessed Residual Cancer Burden (RCB).

Eligibility criteria: Inclusion Criteria:

* Women with histologically proven invasive breast cancer and no distant metastases and;
* Lymphnode negative and a clinical tumor classification of T2 (≥3.5cm)-T4 or with 1-3 positive lymph nodes and a clinical tumor classification of T2-T4 DCIS or LCIS are allowed in addition to invasive cancer at T2 or T3 level.
* Age ≥ 18 years.
* At least one lesion that can be accurately measured in two dimensions utilizing mammogram, ultrasound, or MRI images to define specific size and validate complete pathologic response.
* Adequate bone marrow reserves (neutrophil count \>1.5 x109 /l and platelet count \>100 x109/l), adequate renal function (serum creatinine ≤ 1.5 x upper limit of normal) and hepatic function (ALAT, ASAT ≤ 2.5 x upper limit of normal, alkaline phosphatase ≤ 2.5 x upper limit of normal and total bilirubin ≤ 2.0 x upper limit of normal).
* Signed informed consent of the patient

Exclusion Criteria:

* Any patient with confirmed metastatic disease. Patients with inflammatory breast cancer.
* Tumor sample shipped to Agendia with ≤ 30% tumor cells or that fails Quality Assurance or Quality Control criteria.
* Patients who have had any prior chemotherapy, radiotherapy, or endocrine therapy for the treatment of breast cancer.
* Any serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease.

Primary outcomes:
measure: Determine the predictive power of chemosensitivity of MammaPrint as measured by pCR.
timeFrame: 6-12 months
measure: Determine the predictive power of chemosensitivity of the combination of MammaPrint and BluePrint as measured by pCR.
timeFrame: 6-12 months
Secondary outcomes:
measure: Compare TargetPrint single gene read out of ER, PR and HER2 with local and centralized IHC and/or CISH/FISH assessment of ER, PR and HER2.
timeFrame: Baseline. First study visit.
measure: Identify possible correlations between the TheraPrint Research Gene Panel outcomes and chemoresponsiveness.
timeFrame: 6-9 months
measure: Identify and/or validate predictive gene expression profiles of clinical response/resistance to chemotherapy.
timeFrame: 6-12 months
measure: Compare the three BluePrint molecular subtype categories with IHC-based subtype classification.
timeFrame: Baseline. First study visit.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama, Mitchell Cancer Institute
state: Alabama
city: Clearwater
country: United States
facility: Morton Plant Mease Health Care
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida Breast Cancer Program
state: Florida
city: Tarpon Springs
country: United States
facility: Helen Ellis Memorial Hospital
state: Florida
city: Bronx
country: United States
facility: Eastchester Center for Cancer Care
state: New York
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma, Health Sciences Center
state: Oklahoma
city: Plano
country: United States
facility: Texas Health, Plano Cancer Institute
state: Texas
Study officials:
affiliation: University of South Florida
name: Charles E Cox, MD
role: PRINCIPAL_INVESTIGATOR
References: