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

NCT ID: NCT01501487

Last Updated: 2018-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 226 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2017-06-30

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).

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

HER2 negative patients

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

Group Type: ACTIVE_COMPARATOR

TAC chemotherapy

Intervention Type: DRUG

Docetaxel 75 mg/m2 IV day 1, Doxorubicin 50 mg/m2 IV day 1, Cyclophosphamide 500 mg/m2 IV day 1; Cycled every 21 days for 6 cycles

TC chemotherapy

Intervention Type: DRUG

Docetaxel 75 mg/m2 IV day 1, Cyclophosphamide 600 mg/m2 IV day 1; Cycled every 21 days for 6 cycles

Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy

Intervention Type: DRUG

Doxorubicin 60 mg/m2 IV day 1, Cyclophosphamide 600 mg/m2 IV day 1, Cycled every 14 days for 4 cycles, OR 5-Fluorouracil 500 mg/m2 IV day 1, Epirubicin 100 mg/m2 IV day 1, Cyclophosphamide 500 mg/m2 IV day 1; Cycled every 21 days for 3 cycles Followed by Paclitaxel 80 mg/m2 by 1 h IV infusion weekly for 12 weeks, OR Docetaxel 100mg/m2 IV day 1 cycled every 21 days for 3 or 4 cycles

Her2 positive patients

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

Group Type: ACTIVE_COMPARATOR

TCH chemotherapy

Intervention Type: DRUG

Docetaxel 75 mg/m2 IV day 1, followed by Carboplatin AUC 6 IV day 1; Cycled every 21 days for 6 cycles Trastuzumab initial dose of 4 mg/kg over 90 minute IV infusion, then 2 mg/kg over 30 minute IV infusion weekly for 52 weeks, OR initial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30-90 minutes IV infusion every three weeks for 52 weeks.

T + trastuzumab followed by CEF + trastuzumab

Intervention Type: DRUG

Trastuzumab 4 mg/kg IV for one dose beginning just prior to first dose of paclitaxel.

Followed by trastuzumab 2 mk/kg IV weekly for 23 weeks Paclitaxel 80 mg/m2 by 1 h IV infusion weekly for 12 wks Followed by 5-Fluorouracil 500 mg/m2 IV on days 1 and 4 Epirubicin 75 mg/m2 IV on day 1 Cyclophosphamide 500 mg/m2 IV on day 1 cycled every 21 days for 4 cycles Trastuzumab 6mg/kg IV every 21 days for 9 cycles to complete 1yr

Dose dense AC followed by T + trastuzumab

Intervention Type: DRUG

Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 (cycled every 14 days for 4 cycles) Followed by paclitaxel 80 mg/m2 by 1 h IV infusion weekly for 12 wks All cycles are with filgrastim support with trastuzumab 2 mg/kg (4 mg/kg loading dose).

Following chemotherapy , trastuzumab to continue every 3 weeks at 6 mg/kg for the duration of 1 week.

Dose dense AC followed by T + trastuzumab + pertuzumab

Intervention Type: DRUG

Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Cycled every 14 days for 4 cycles Followed by docetaxel 75-100 mg/m2 by 1 h IV infusion weekly for 12 wks All cycles are with filgrastim support with trastuzumab 6 mg/kg (8 mg/kg loading dose with C1) Pertuzumab 420 mg (840 mg loading dose with C1). Following chemotherapy, trastuzumab to continue every 3 weeks at 6 mg/kg for the duration of 1 week.

PTH followed by dose dense AC of FEC

Intervention Type: DRUG

Docetaxel 75-100 mg/m2 by 1 h IV infusion Cycled every 21 days for 4 cycles With Trastuzumab 6 mg/kg IV (8 mg/kg IV loading dose) q3W And Pertuzumab 420 mg IV (840 mg IV loading dose) q 3w +/- pegfilgrastim 6 mg sq on day 2-3,

Followed by 4 cycles of AC or FEC:

AC Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Cycled every 14 days for 4 cycles with pegfilgrastim 6 mg sq on day 2 FEC 5-Fluorouracil 500 mg/m2 IV on days 1 and 4 Epirubicin 75 mg/m2 IV on day 1 Cyclophosphamide 500 mg/m2 IV on day 1 cycled every 21 days for 4 cycles

In all of the above mentioned regimens docetaxel might be substituted with paclitaxel as paclitaxel is better tolerated but is expected to have the same efficacy as docetaxel.

Interventions

TAC chemotherapy

Docetaxel 75 mg/m2 IV day 1, Doxorubicin 50 mg/m2 IV day 1, Cyclophosphamide 500 mg/m2 IV day 1; Cycled every 21 days for 6 cycles

Intervention Type: DRUG

TC chemotherapy

Docetaxel 75 mg/m2 IV day 1, Cyclophosphamide 600 mg/m2 IV day 1; Cycled every 21 days for 6 cycles

Intervention Type: DRUG

Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy

Doxorubicin 60 mg/m2 IV day 1, Cyclophosphamide 600 mg/m2 IV day 1, Cycled every 14 days for 4 cycles, OR 5-Fluorouracil 500 mg/m2 IV day 1, Epirubicin 100 mg/m2 IV day 1, Cyclophosphamide 500 mg/m2 IV day 1; Cycled every 21 days for 3 cycles Followed by Paclitaxel 80 mg/m2 by 1 h IV infusion weekly for 12 weeks, OR Docetaxel 100mg/m2 IV day 1 cycled every 21 days for 3 or 4 cycles

Intervention Type: DRUG

TCH chemotherapy

Docetaxel 75 mg/m2 IV day 1, followed by Carboplatin AUC 6 IV day 1; Cycled every 21 days for 6 cycles Trastuzumab initial dose of 4 mg/kg over 90 minute IV infusion, then 2 mg/kg over 30 minute IV infusion weekly for 52 weeks, OR initial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30-90 minutes IV infusion every three weeks for 52 weeks.

Intervention Type: DRUG

T + trastuzumab followed by CEF + trastuzumab

Trastuzumab 4 mg/kg IV for one dose beginning just prior to first dose of paclitaxel.

Followed by trastuzumab 2 mk/kg IV weekly for 23 weeks Paclitaxel 80 mg/m2 by 1 h IV infusion weekly for 12 wks Followed by 5-Fluorouracil 500 mg/m2 IV on days 1 and 4 Epirubicin 75 mg/m2 IV on day 1 Cyclophosphamide 500 mg/m2 IV on day 1 cycled every 21 days for 4 cycles Trastuzumab 6mg/kg IV every 21 days for 9 cycles to complete 1yr

Intervention Type: DRUG

Dose dense AC followed by T + trastuzumab

Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 (cycled every 14 days for 4 cycles) Followed by paclitaxel 80 mg/m2 by 1 h IV infusion weekly for 12 wks All cycles are with filgrastim support with trastuzumab 2 mg/kg (4 mg/kg loading dose).

Following chemotherapy , trastuzumab to continue every 3 weeks at 6 mg/kg for the duration of 1 week.

Intervention Type: DRUG

Dose dense AC followed by T + trastuzumab + pertuzumab

Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Cycled every 14 days for 4 cycles Followed by docetaxel 75-100 mg/m2 by 1 h IV infusion weekly for 12 wks All cycles are with filgrastim support with trastuzumab 6 mg/kg (8 mg/kg loading dose with C1) Pertuzumab 420 mg (840 mg loading dose with C1). Following chemotherapy, trastuzumab to continue every 3 weeks at 6 mg/kg for the duration of 1 week.

Intervention Type: DRUG

PTH followed by dose dense AC of FEC

Docetaxel 75-100 mg/m2 by 1 h IV infusion Cycled every 21 days for 4 cycles With Trastuzumab 6 mg/kg IV (8 mg/kg IV loading dose) q3W And Pertuzumab 420 mg IV (840 mg IV loading dose) q 3w +/- pegfilgrastim 6 mg sq on day 2-3,

Followed by 4 cycles of AC or FEC:

AC Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Cycled every 14 days for 4 cycles with pegfilgrastim 6 mg sq on day 2 FEC 5-Fluorouracil 500 mg/m2 IV on days 1 and 4 Epirubicin 75 mg/m2 IV on day 1 Cyclophosphamide 500 mg/m2 IV on day 1 cycled every 21 days for 4 cycles

In all of the above mentioned regimens docetaxel might be substituted with paclitaxel as paclitaxel is better tolerated but is expected to have the same efficacy as docetaxel.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of South Florida

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

Morton Plant Mease Health Care

OTHER

Sponsor Role: collaborator

AdventHealth

OTHER

Sponsor Role: collaborator

Plano Cancer Center

UNKNOWN

Sponsor Role: collaborator

Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role: collaborator

University of Oklahoma

OTHER

Sponsor Role: collaborator

University of South Alabama

OTHER

Sponsor Role: collaborator

Agendia

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles E Cox, MD

Role: PRINCIPAL_INVESTIGATOR

University of South Florida

Locations

University of South Alabama, Mitchell Cancer Institute

Mobile, Alabama, United States

Morton Plant Mease Health Care

Clearwater, Florida, United States

University of Miami

Miami, Florida, United States

University of South Florida Breast Cancer Program

Tampa, Florida, United States

Helen Ellis Memorial Hospital

Tarpon Springs, Florida, United States

Eastchester Center for Cancer Care

The Bronx, New York, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

University of Oklahoma, Health Sciences Center

Oklahoma City, Oklahoma, United States

Texas Health, Plano Cancer Institute

Plano, Texas, United States

Countries

United States

Other Identifiers

P0334

Identifier Type: -

Identifier Source: org_study_id