MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I

Phase 4

Completed

• Conditions: Breast Cancer
• Interventions: Drug: TAC chemotherapy; Drug: TCH chemotherapy; Drug: TC chemotherapy; Drug: T + trastuzumab followed by CEF + trastuzumab; Drug: Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy; Drug: Dose dense AC followed by T + trastuzumab; Drug: Dose dense AC followed by T + trastuzumab + pertuzumab; Drug: PTH followed by dose dense AC of FEC

• Registration Number: NCT01501487
• Lead Sponsor: Agendia

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).

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-12-22
• Study First Submitted QC: 2011-12-27
• Study First Posted: 2011-12-29
• Primary Completion: 2016-02
• Study Completion: 2017-06
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-26
• Last Update Posted: 2018-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 226

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HER2 negative patients	TAC chemotherapy	In order to provide some consistency in management and have a treatment policy in place only recommended therapy with several well accepted and presumed equivalent chemotherapy regimens will be used. The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients include: 1. TAC chemotherapy 2. TC chemotherapy 3. Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy
HER2 negative patients	TC chemotherapy	In order to provide some consistency in management and have a treatment policy in place only recommended therapy with several well accepted and presumed equivalent chemotherapy regimens will be used. The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients include: 1. TAC chemotherapy 2. TC chemotherapy 3. Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy
HER2 negative patients	Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy	In order to provide some consistency in management and have a treatment policy in place only recommended therapy with several well accepted and presumed equivalent chemotherapy regimens will be used. The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients include: 1. TAC chemotherapy 2. TC chemotherapy 3. Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy
Her2 positive patients	TCH chemotherapy	The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients is TCH chemotherapy.
Her2 positive patients	T + trastuzumab followed by CEF + trastuzumab	The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients is TCH chemotherapy.
Her2 positive patients	Dose dense AC followed by T + trastuzumab	The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients is TCH chemotherapy.
Her2 positive patients	Dose dense AC followed by T + trastuzumab + pertuzumab	The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients is TCH chemotherapy.
Her2 positive patients	PTH followed by dose dense AC of FEC	The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients is TCH chemotherapy.

Primary Outcome Measures

Name	Time	Method
Determine the predictive power of chemosensitivity of MammaPrint as measured by pCR.	6-12 months
Determine the predictive power of chemosensitivity of the combination of MammaPrint and BluePrint as measured by pCR.	6-12 months

Secondary Outcome Measures

Name	Time	Method
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.	Baseline. First study visit.
Identify possible correlations between the TheraPrint Research Gene Panel outcomes and chemoresponsiveness.	6-9 months
Identify and/or validate predictive gene expression profiles of clinical response/resistance to chemotherapy.	6-12 months
Compare the three BluePrint molecular subtype categories with IHC-based subtype classification.	Baseline. First study visit.

Trial Locations

Locations (9)

University of Miami; 🇺🇸 Miami, Florida, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

University of South Alabama, Mitchell Cancer Institute; 🇺🇸 Mobile, Alabama, United States

University of South Florida Breast Cancer Program; 🇺🇸 Tampa, Florida, United States

Texas Health, Plano Cancer Institute; 🇺🇸 Plano, Texas, United States

University of Oklahoma, Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Morton Plant Mease Health Care; 🇺🇸 Clearwater, Florida, United States

Helen Ellis Memorial Hospital; 🇺🇸 Tarpon Springs, Florida, United States

Eastchester Center for Cancer Care; 🇺🇸 Bronx, New York, United States