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Genetic Testing or Clinical Assessment in Determining the Need for Chemotherapy in Women With Breast Cancer That Involves No More Than 3 Lymph Nodes

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00433589
First received: February 8, 2007
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving chemotherapy and hormone therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether genetic testing is more effective than clinical assessment in determining the need for chemotherapy in treating breast cancer.

PURPOSE: This randomized phase III trial is studying genetic testing to see how well it works compared with clinical assessment in determining the need for chemotherapy in women with breast cancer that is either node-negative or involves no more than 3 lymph nodes.


Condition Intervention Phase
Breast Cancer
Drug: capecitabine
Drug: cyclophosphamide
Drug: docetaxel
Drug: doxorubicin hydrochloride
Drug: epirubicin hydrochloride
Drug: fluorouracil
Drug: letrozole
Drug: methotrexate
Drug: tamoxifen citrate
Procedure: adjuvant therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MINDACT (Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy): A Prospective, Randomized Study Comparing the 70-Gene Signature With the Common Clinical-Pathological Criteria in Selecting Patients for Adjuvant Chemotherapy in Breast Cancer With 0 to 3 Positive Nodes

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Distant metastasis-free survival at 5 years [ Time Frame: from enrollment/randomization ] [ Designated as safety issue: No ]
  • Disease-free survival (DFS) [ Time Frame: from enrollment/randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients treated with chemotherapy based on clinical prognosis compared to 70-gene signature prognosis [ Time Frame: from enrollment ] [ Designated as safety issue: No ]
  • Overall survival at 5 years [ Time Frame: from enrollment/randomization ] [ Designated as safety issue: No ]
  • DFS at 5 years [ Time Frame: from enrollment/randomization ] [ Designated as safety issue: No ]
  • Safety (early and late) [ Time Frame: from registration ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 6600
Study Start Date: December 2006
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer meeting the following criteria:

    • T1, T2, or operable T3 disease
    • Zero to three positive lymph nodes and no distant metastases
    • Unilateral tumor

      • Multifocal tumors are allowed provided that they have identical histology
      • Ductal carcinoma in situ or lobular carcinoma in situ allowed
  • Operable disease

    • Must have undergone breast-conserving surgery or mastectomy with either a sentinel node procedure or full axillary clearance

      • Radiotherapy is mandatory in the case of breast-conserving surgery
      • Unresectable positive deep margins and will receive adjuvant radiotherapy provided that all other margins negative allowed
  • Patients eligible for inclusion in the chemotherapy randomization must meet one of the following criteria:

    • High-risk of recurrence according to both the clinical-pathological criteria and the 70-gene signature
    • High risk of recurrence according to the clinical-pathological criteria and low-risk of recurrence according to the 70-gene signature and are randomized to use the clinical-pathological criteria for chemotherapy decision
    • Low-risk of recurrence according to the clinical-pathological criteria and high-risk of recurrence according to the 70-gene signature and are randomized to use the 70-gene signature for chemotherapy decision
  • Patients eligible for inclusion in the endocrine therapy randomization must meet all of the following criteria:

    • Endocrine-responsive disease
    • Hormone receptor-positive disease (estrogen receptor-positive, progesterone receptor-positive, or both)

PATIENT CHARACTERISTICS:

  • Female
  • WHO performance status 0-1
  • Neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Creatinine clearance at least 50 mL/min OR creatinine up to 1.5 times upper limit of normal (ULN)
  • ALT and AST up to 2.5 times ULN
  • Alkaline phosphatase up to 2.5 times ULN
  • Bilirubin up to 2.0 times ULN
  • Normal echocardiogram (ECHO) compatible with chemotherapy treatment
  • No serious cardiac illness or medical condition including, but not limited to, any of the following:

    • History of documented congestive heart failure
    • High-risk uncontrolled arrhythmias
    • Angina pectoris requiring antianginal medication
    • Clinically significant valvular heart disease
    • Evidence of transmural infarction on ECG
    • Poorly controlled hypertension (e.g., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
    • Symptomatic coronary artery disease or a myocardial infarction within the past 12 months
    • Other risk factors that contraindicate the use of anthracycline-based chemotherapy
  • No serious uncontrolled infection or other serious uncontrolled disease
  • No other cancer within the past 5 years except for adequately treated carcinoma in situ of the cervix, nonmelanoma skin cancer, lobular or ductal carcinoma in situ of the breast, or any invasive cancer (other than breast cancer)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception
  • No psychological, familial, sociological, or geographical condition that would preclude study treatment
  • No psychiatric disability
  • No history of uncontrolled seizures or CNS disorders
  • Patients eligible for inclusion in the chemotherapy randomization must meet all of the following additional criteria:

    • LVEF normal by ECHO or MUGA
    • No prior severe hypersensitivity reaction to drugs formulated with polysorbate 80
    • Must have physical integrity of the upper gastrointestinal tract
    • Able to swallow tablets
    • No malabsorption syndrome
  • No prior thromboembolic disorder, deep vein thrombosis, or pulmonary emboli (for patients eligible for inclusion in the endocrine therapy randomization)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior neoadjuvant chemotherapy, neoadjuvant endocrine therapy, or radiotherapy for primary breast cancer
  • No participation in another investigational drug study within the past 4 weeks
  • No systemic hormone replacement therapy (with or without progestins) for more than 3 months in duration
  • Patients eligible for inclusion in the chemotherapy randomization must meet all of the following additional criteria:

    • Interval between definitive surgery and start of chemotherapy 8-18 weeks
    • No prior organ allografts requiring immunosuppressive therapy
    • No concurrent sorivudine or chemically related analogues, such as brivudine
  • Patients eligible for inclusion in the endocrine therapy randomization must meet all of the following additional criteria:

    • No prior high-dose systemic corticosteroids (except as antiemetic treatment), immunotherapy, or biological response modifiers (e.g., interferon)
    • No prior adjuvant antiestrogen therapy for > 1 month immediately after surgery, radiotherapy, and/or chemotherapy
    • No hormone replacement therapy within the past 4 weeks
    • No antiestrogens (e.g., tamoxifen or raloxifen) as chemoprevention or osteoporosis treatment for breast cancer within the past 18 months
  • No concurrent primary prophylaxis with filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim
  • No other concurrent treatment during endocrine therapy, including the following:

    • Anticancer therapy (anti-estrogens, aromatase inhibitors, chemotherapy)
    • Investigational agents
    • Raloxifene or other selective estrogen-receptor modulators
    • Hormonal contraceptives (including depot injections and implants)

      • Intrauterine devices, including progesterone-coated, allowed
    • Oral or transdermal hormonal treatments, including estrogen, progesterone, androgen, or aromatase inhibitor

      • Local vaginal (topical) estrogens with minimal systemic absorption allowed for severe vaginal dryness/dyspareunia
  • Concurrent bisphosphonates allowed
  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: NCT00433589

Locations
Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066 CX
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Emiel J. T. Rutgers, MD, PhD, FRCS The Netherlands Cancer Institute
Study Chair: Martine J. Piccart-Gebhart, MD, PhD Institut Jules Bordet
Study Chair: Fatima Cardoso, MD Champalimaud Cancer Center, Lisbon Portugal
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00433589     History of Changes
Other Study ID Numbers: EORTC-10041, 2005-002625-31, BIG-3-04, EU-20676, NOVARTIS-EORTC-10041, ROCHE-EORTC-10041, SANOFI-AVENTIS-EORTC-10041
Study First Received: February 8, 2007
Last Updated: January 10, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Slovenia: Agency for Medicinal Products - Ministry of Health
Slovenia: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Councils UK

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
invasive ductal breast carcinoma
invasive lobular breast carcinoma
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
estrogen receptor-positive breast cancer
progesterone receptor-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Cyclophosphamide
Doxorubicin
Epirubicin
Fluorouracil
Liposomal doxorubicin
Methotrexate
Tamoxifen
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Bone Density Conservation Agents
Dermatologic Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Folic Acid Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on November 25, 2014