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

Agendia

Status and phase: Completed; Phase 4

Conditions: Breast Cancer

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01501487

P0334

Details and patient eligibility

About

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).

Full 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).

Enrollment: 226 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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226 participants in 2 patient groups

HER2 negative patients

Active Comparator group

Description:

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

Treatment:

Drug: Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy

Drug: TC chemotherapy

Drug: TAC chemotherapy

Her2 positive patients

Active Comparator group

Description:

The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients is TCH chemotherapy.

Treatment:

Drug: PTH followed by dose dense AC of FEC

Drug: Dose dense AC followed by T + trastuzumab + pertuzumab

Drug: T + trastuzumab followed by CEF + trastuzumab

Drug: TCH chemotherapy

Drug: Dose dense AC followed by T + trastuzumab