Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Agendia
Sponsor:
Collaborators:
University of South Florida
University of Miami
Morton Plant Mease Health Care
Helen Ellis Memorial Hospital
Texas Health Plano Cancer Institute
Ohio State University Comprehensive Cancer Center
University of Oklahoma
Eastchester Center for Cancer Care
University of Southern Alabama
Information provided by (Responsible Party):
Agendia
ClinicalTrials.gov Identifier:
NCT01501487
First received: December 22, 2011
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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).


Condition Intervention Phase
Breast Cancer
Drug: TAC chemotherapy
Drug: TC chemotherapy
Drug: Dose Dense AC or FEC100 followed by paclitaxel or docetaxel 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
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I

Resource links provided by NLM:


Further study details as provided by Agendia:

Primary Outcome Measures:
  • Determine the predictive power of chemosensitivity of MammaPrint as measured by pCR. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
  • Determine the predictive power of chemosensitivity of the combination of MammaPrint and BluePrint as measured by pCR. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Baseline. First study visit. ] [ Designated as safety issue: No ]
  • Identify possible correlations between the TheraPrint Research Gene Panel outcomes and chemoresponsiveness. [ Time Frame: 6-9 months ] [ Designated as safety issue: No ]
  • Identify and/or validate predictive gene expression profiles of clinical response/resistance to chemotherapy. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
  • Compare the three BluePrint molecular subtype categories with IHC-based subtype classification. [ Time Frame: Baseline. First study visit. ] [ Designated as safety issue: No ]

Estimated Enrollment: 226
Study Start Date: October 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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
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
Drug: TC chemotherapy
Docetaxel 75 mg/m2 IV day 1, Cyclophosphamide 600 mg/m2 IV day 1; Cycled every 21 days for 6 cycles
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
Active Comparator: Her2 positive patients
The proposed neo-adjuvant chemotherapy regimens for HER2 negative patients is TCH chemotherapy.
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.
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

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.

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.
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.


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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01501487

Contacts
Contact: Erin B Yoder, MS erin.yoder@agendia.com
Contact: Lisette Stork, MSc lisette.stork@agendia.com

Locations
United States, Alabama
University of South Alabama, Mitchell Cancer Institute Recruiting
Mobile, Alabama, United States, 36688
Contact: Austin Cadden, MBA, MPH    251-445-8427    jcadden@health.southalabama.edu   
Contact: Pat Shaw    (251) 445-8353    pshaw@health.southalabama.edu   
Principal Investigator: Lynn Dyess, MD         
United States, Florida
Morton Plant Mease Health Care Recruiting
Clearwater, Florida, United States, 33756
Contact: Peter Blumencranz, MD    727-461-8526      
Contact: Debbie Ellis    727-461-8526    Debra.Ellis@baycare.org   
Principal Investigator: Peter Blumencranz, MD         
University of Miami Recruiting
Miami, Florida, United States, 33124
Contact: Lily Sanchez    305-243-7912    Lsanchez@med.miami.edu   
Contact: Lynne Sparling       LSparlin@med.miami.edu   
Principal Investigator: Eli Avisar, MD         
University of South Florida Breast Cancer Program Recruiting
Tampa, Florida, United States, 33613
Contact: Charles Cox, MD    813-396-2483    coxce@hotmail.com   
Contact: Michelle Jung    (813) 793-4272 ext 208    mjung@health.usf.edu   
Principal Investigator: Charles Cox, MD         
Helen Ellis Memorial Hospital Recruiting
Tarpon Springs, Florida, United States, 34689
Contact: Douglas Reintgen, MD    727-942-5000    dreintge@health.usf.edu   
Principal Investigator: Douglas Reintgen, MD         
United States, New York
Eastchester Center for Cancer Care Recruiting
Bronx, New York, United States, 10469
Contact: Carmen Vicuna       carmen@eastchestercenter.com   
Principal Investigator: Karen Hoffman, MD         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43212
Contact: Laura Reebel    614-366-7994    Laura.Reebel@osumc.edu   
Contact: Dan Saluke    (614) 688-7561    Dan.Saluke@osumc.edu   
Principal Investigator: Robert Wesolowski, MD         
United States, Oklahoma
University of Oklahoma, Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Michelle Stephens, RN       michelle-stephens@ouhsc.edu   
Contact: Shartory Simms       shartory-simms@ouhsc.edu   
Principal Investigator: William Dooley, MD         
United States, Texas
Texas Health, Plano Cancer Institute Recruiting
Plano, Texas, United States, 75093
Contact: Ruben Saez, MD       RubenSaez@texashealth.org   
Contact: Suzette Clark    (214) 483-6933    suzetteclark@texashealth.org   
Principal Investigator: Ruben Saez, MD         
Sponsors and Collaborators
Agendia
University of South Florida
University of Miami
Morton Plant Mease Health Care
Helen Ellis Memorial Hospital
Texas Health Plano Cancer Institute
Ohio State University Comprehensive Cancer Center
University of Oklahoma
Eastchester Center for Cancer Care
University of Southern Alabama
Investigators
Principal Investigator: Charles E Cox, MD University of South Florida
  More Information

Additional Information:
No publications provided

Responsible Party: Agendia
ClinicalTrials.gov Identifier: NCT01501487     History of Changes
Other Study ID Numbers: P0334
Study First Received: December 22, 2011
Last Updated: October 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Agendia:
breast cancer
neo adjuvant therapy

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Docetaxel
Paclitaxel
Pertuzumab
Trastuzumab
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014