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

NCT01501487 | Completed Phase 4

• 1 other identifier: P0334
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 9

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).

Conditions

Breast Cancer

Keywords

breast cancer; neo adjuvant therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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.

Study Arms (2)

HER2 negative patients

ACTIVE COMPARATOR

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

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

Her2 positive patients

ACTIVE COMPARATOR

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

Drug: TCH chemotherapy; Drug: T + trastuzumab followed by CEF + trastuzumab; 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

Interventions

TAC chemotherapy 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

HER2 negative patients

TC chemotherapy DRUG

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

HER2 negative patients

Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy 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 negative patients

TCH chemotherapy 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.

Her2 positive patients

T + trastuzumab followed by CEF + trastuzumab 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

Her2 positive patients

Dose dense AC followed by T + trastuzumab 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.

Her2 positive patients

Dose dense AC followed by T + trastuzumab + pertuzumab 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.

Her2 positive patients

PTH followed by dose dense AC of FEC 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.

Her2 positive patients

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Agendia: lead
• University of South Florida: collaborator
• University of Miami: collaborator
• Morton Plant Mease Health Care: collaborator
• AdventHealth: collaborator
• Plano Cancer Center: collaborator
• Ohio State University Comprehensive Cancer Center: collaborator
• University of Oklahoma: collaborator
• University of South Alabama: collaborator

Study Sites (9)

University of South Alabama, Mitchell Cancer Institute

Mobile, Alabama, 36688, United States

Location

Morton Plant Mease Health Care

Clearwater, Florida, 33756, United States

Location

University of Miami

Miami, Florida, 33124, United States

Location

University of South Florida Breast Cancer Program

Tampa, Florida, 33613, United States

Location

Helen Ellis Memorial Hospital

Tarpon Springs, Florida, 34689, United States

Location

Eastchester Center for Cancer Care

The Bronx, New York, 10469, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43212, United States

Location

University of Oklahoma, Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Texas Health, Plano Cancer Institute

Plano, Texas, 75093, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Charles E Cox, MD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 29, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2016
• Study Completion: June 1, 2017
• Last Updated: June 28, 2018

Record last verified: 2018-06

Locations

US (9)