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

Breast Cancer Clinical Trial

— MINT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01501487
• Other study ID #: P0334
• Status: Completed
• Phase: Phase 4
• Start date: October 2011
• Est. completion date: June 2017

Study information

• Verified date: June 2018
• Source: Agendia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: June 2017
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer

Intervention

Drug:
• 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
• TC chemotherapy
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
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
• 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.
• 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
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Morton Plant Mease Health Care	Clearwater	Florida
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	University of Miami	Miami	Florida
United States	University of South Alabama, Mitchell Cancer Institute	Mobile	Alabama
United States	University of Oklahoma, Health Sciences Center	Oklahoma City	Oklahoma
United States	Texas Health, Plano Cancer Institute	Plano	Texas
United States	University of South Florida Breast Cancer Program	Tampa	Florida
United States	Helen Ellis Memorial Hospital	Tarpon Springs	Florida

Sponsors (9)

Lead Sponsor	Collaborator
Agendia	Florida Hospital, Morton Plant Mease Health Care, Ohio State University Comprehensive Cancer Center, Plano Cancer Center, University of Miami, University of Oklahoma, University of South Alabama, University of South Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the predictive power of chemosensitivity of MammaPrint as measured by pCR.		6-12 months
Primary	Determine the predictive power of chemosensitivity of the combination of MammaPrint and BluePrint as measured by pCR.		6-12 months
Secondary	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.
Secondary	Identify possible correlations between the TheraPrint Research Gene Panel outcomes and chemoresponsiveness.		6-9 months
Secondary	Identify and/or validate predictive gene expression profiles of clinical response/resistance to chemotherapy.		6-12 months
Secondary	Compare the three BluePrint molecular subtype categories with IHC-based subtype classification.		Baseline. First study visit.