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Phase III Randomized Study of 70-Gene Signature Versus Clinical Assessment in Selecting Women With Node-Negative Breast Cancer for Adjuvant Chemotherapy
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Registry Information
Alternate Title
Genetic Testing or Clinical Assessment in Determining the Need for Chemotherapy in Women With Node-Negative Breast Cancer
Basic Trial Information
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Protocol IDs
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Phase III
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Treatment
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Active
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18 to 70
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Other, Pharmaceutical / Industry
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EORTC-10041 EUDRACT-2005-002625-31, BIG-3-04, NOVARTIS-EORTC-10041, ROCHE-EORTC-10041, SANOFI-AVENTIS-EORTC-10041, NCT00433589
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Objectives Primary - Compare a molecular
profiling approach (70-gene signature) vs usual clinical assessment in assigning adequate risk categories (and the
need to receive adjuvant chemotherapy or not) to breast cancer patients with 0-3 positive lymph nodes.
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Compare the efficacy and long-term toxicities of docetaxel and capecitabine vs standard anthracycline-based
chemotherapy regimens in these patients.
- Determine the best endocrine treatment strategy (i.e., letrozole for 7 years vs sequential tamoxifen for 2 years followed by letrozole for 5 years) in these patients.
Secondary - Compare both relative (hazard ratio) and absolute (percentage at 5 years) efficacy of these regimens, in terms of
disease-free survival (DFS), distant metastasis-free survival (DMFS) and overall survival (OS), in these patients.
- Determine overall estimates of efficacy (DFS, DMFS, OS) for each treatment strategy
according to clinical-pathological prognosis and molecular prognosis in these patients.
- Estimate the percentage of patients receiving chemotherapy per each prognostic method.
- Identify predictive gene expression profiles of clinical response/resistance to
anthracycline-based and docetaxel-capecitabine chemotherapy in these patients.
- Compare novel gene expression signatures predicting clinical response in patients treated with sequential tamoxifen-letrozole vs letrozole alone.
- Compare the OS distributions in patients treated with these regimens.
- Compare the early and late toxicities of these regimens in these patients.
- Evaluate adjuvant endocrine treatment success or failure in the subgroup of postmenopausal
patients with endocrine-responsive disease.
- Compare the safety profile of these two endocrine therapy regimens in these patients.
Entry 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 if invasive cancer is
present
- 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 adjuvant radiotherapy with 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)
Prior/Concurrent Therapy:
- See Disease Characteristics
- No prior chemotherapy, hormonal therapy, or radiotherapy
- 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 6-8 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 as chemoprevention 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
Patient Characteristics:
- Female
- WHO performance status 0-1
- Neutrophil count > 1,500/mm3
- Platelet count > 100,000/mm3
- 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 invasive cancer within the past 5 years except for adequately treated carcinoma
in situ of the cervix or nonmelanoma skin 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)
Expected Enrollment 6000A total of 6,000 patients will be accrued for this study. Outcomes Primary Outcome(s)Distant metastasis-free survival at 5 years Disease-free survival (DFS)
Secondary Outcome(s)Proportion of patients treated with chemotherapy based on clinical prognosis compared to 70-gene signature prognosis Overall survival at 5 years DFS at 5 years Safety (early and late)
Outline This is a partially randomized, open-label, prospective, multicenter study. Patients with both clinical high-risk (CHR) and genomic high-risk (GHR) disease are assigned to receive chemotherapy. Patients with both clinical low-risk (CLR) and genomic low-risk (GLR) disease do not receive chemotherapy. Patients with discordant risk between the 2 decision-making tools (standard clinical-pathological criteria vs 70-gene signature criteria) are randomized to receive chemotherapy or not. After completion of study treatment, patients are followed annually for at least 15 years.
Trial Contact Information
Trial Lead Organizations European Organization for Research and Treatment of Cancer | | | Emiel Rutgers, MD, PhD, FRCS, Study coordinator | | | | Martine Piccart-Gebhart, MD, PhD, Study coordinator | | | | Fatima Cardoso, MD, Study coordinator | | | | Trial Sites
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Netherlands |
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Amsterdam |
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| | | Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital |
| | Emiel Rutgers, MD, PhD, FRCS | |
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Registry Information | | Official Title | | MINDACT (Microarray In Node-negative 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 Node-Negative Breast Cancer | | Trial Start Date | | 2006-12-07 | | Trial Completion Date | | 2019-03-30 (estimated) | | Registered in ClinicalTrials.gov | | NCT00433589 | | Date Submitted to PDQ | | 2006-12-11 | | Information Last Verified | | 2008-06-18 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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