MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I - Full Text View

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	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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Phenylephrine Phenylephrine hydrochloride Triamcinolone diacetate Triamcinolone acetonide Triamcinolone Oxymetazoline Oxymetazoline hydrochloride Triamcinolone hexacetonide Paclitaxel Docetaxel

U.S. FDA Resources

Further study details as provided by Agendia:

Primary Outcome Measures:

Difference in response rate in the molecular subtype categories. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Difference between single gene read out of ER, PR and HER2 and local and centralized immunohistochemistry (IHC) and/or CISH/FISH assessment of ER, PR and HER2. [ Time Frame: Baseline. First study visit. ] [ Designated as safety issue: No ]
Identification and/or validation of predictive gene expression profiles of clinical response/resistance to chemotherapy. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
Response rate of TheraPrint Research Gene Panel. [ Time Frame: 6-9 months ] [ Designated as safety issue: No ]
Difference between molecular subtype classification (BluePrint) and immunohistochemistry 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 2013
Estimated Primary Completion Date:	December 2013 (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: TAC chemotherapy TC chemotherapy 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.

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:

TAC chemotherapy
TC chemotherapy
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.

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:

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
Neo-adjuvant chemotherapy
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 Responce (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

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

Locations

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 South Florida Breast Cancer Program	Recruiting
Tampa, Florida, United States, 33613
Contact: Charles Cox, MD 813-396-2483 coxce@hotmail.com
Principal Investigator: Charles Cox, MD
United States, Texas
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

Investigators

Principal Investigator:

Charles Cox, MD

University of South Florida

More 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:	January 16, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Agendia:

breast cancer
neo adjuvant therapy

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adjuvants, Immunologic
Paclitaxel
Docetaxel
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013