Clinical Trials (PDQ®)
|No phase specified||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||NCI, Other||MCC-13311|
NCI-2010-02342, P30CA016059, NCT01293032
RATIONALE: DNA analysis of tumor tissue may help doctors predict how well patients will respond to treatment and plan effective treatment.
PURPOSE: This phase II trial is studying how well hormone therapy or chemotherapy before surgery based on gene expression analysis works in treating patients with breast cancer
Further Study Information
I. To determine the feasibility of carrying out a large-scale multi-center trial in which RS would be used to select treatment type in the neoadjuvant setting and whether patients with intermediate RS are willing to be randomized between hormonal and chemotherapy.
II. To determine whether the type of neoadjuvant therapy (hormonal versus cytotoxic chemotherapy) chosen on the basis of gene expression profiling will result in consistently high rates of objective clinical responses in all patients.
III. To determine whether the type of neoadjuvant therapy (hormonal versus cytotoxic chemotherapy) chosen on the basis of gene expression profiling will facilitate planned breast-conserving therapy.
IV. To determine whether choosing the type of neoadjuvant therapy (hormonal versus cytotoxic chemotherapy) on the basis of gene expression profiling will optimize the proportion of patients overall who have a clinical complete response (cCR).
V. To determine whether choosing the type of neoadjuvant therapy (hormonal versus cytotoxic chemotherapy) on the basis of gene expression profiling will optimize the pathologic complete response (pCR) rate in the breast of patients receiving cytotoxic chemotherapy.
VI. To determine whether choosing the type of neoadjuvant therapy (hormonal versus cytotoxic chemotherapy) on the basis of gene expression profiling will optimize the pCR rate in the breast and nodes of patients receiving cytotoxic chemotherapy.
VII. To determine whether choosing the type of neoadjuvant therapy (hormonal versus cytotoxic chemotherapy) on the basis of gene expression profiling will increase the proportion of patients with Class 0 and 1 residual cancer burden (RCB) in patients receiving cytotoxic chemotherapy.
OUTLINE: Patients are assigned to 1 of 3 groups based on recurrence score (RS) following Oncotype Dx gene expression profiling.
GROUP I (Recurrence Score < 11): Patients receive neoadjuvant hormonal therapy comprising tamoxifen (pre-menopausal women) or an aromatase inhibitor (post-menopausal women) for 4-6 months in the absence of disease progression or unacceptable toxicity.
GROUP II (Recurrence Score 11-25): Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive neoadjuvant hormonal therapy as in group I.
ARM II: Patients receive 6-8 courses of neoadjuvant chemotherapy comprising an anthracycline/taxane based regimen over 4-6 months in the absence of disease progression or unacceptable toxicity.
GROUP III (Recurrence Score > 25): Patients receive neoadjuvant chemotherapy as in arm II of group II.
All patients then undergo surgery and receive hormonal therapy for at least 5 years.
After completion of study treatment, patients are followed up periodically.
- The treating surgeon must determine that breast conservation therapy (BCT) would be made more feasible by reducing tumor size using neoadjuvant systemic therapy - The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines
- The patient must be female
- The patient must be greater than or equal to 18 years old
- The patient must have an ECOG performance status of 0 or 1
- The diagnosis of invasive carcinoma of the breast must have been made by core needle biopsy
- The primary breast tumor must be >= 2 cm by physical exam or imaging
- Ipsilateral axillary lymph nodes must be evaluated by imaging (MRI or ultrasound) within 6 weeks prior to randomization; If indicated for abnormal lymph nodes, fine needle aspirate (FNA) or core biopsy must be performed.
- The tumor must have been determined to be HER2-negative as follows: fluorescent in situ hybridization (FISH)-negative (defined by ratio of HER2 to CEP17 must be < 2.2) or, if a ratio was not performed, the HER2 gene copy number must be < 4 per nucleus; or if CISH is performed, the result must indicate a HER2 gene copy number of < 6 per nucleus; or immunohistochemistry (IHC) 0-1+; or IHC 2+ and FISH-negative or CISH-negative
- The tumor must have been determined to be ER+ and/or progesterone positive (PgR+) defined as > 10% tumor staining by immunohistochemistry
- The patient must be considered by the treating medical oncologist to be medically able to tolerate standard cytotoxic chemotherapy regimens
- FNA alone to diagnose the primary tumor
- Excisional biopsy or lumpectomy performed prior to randomization
- Surgical axillary staging procedure or sentinel node (SN) biopsy performed prior to randomization
- Tumors clinically staged as including inflammatory breast cancer
- Ipsilateral cN2b or cN3 disease; (patients with cN1 or cN2a disease are eligible)
- Definitive clinical or radiologic evidence of metastatic disease; (Note: chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 6 weeks prior to randomization)
- Synchronous or metachronous contralateral invasive breast cancer; (patients with synchronous and/or metachronous contralateral DCIS or LCIS are eligible)
- HER2 test result of IHC 3+, regardless of FISH results, if performed
- Any history of ipsilateral invasive breast cancer or ipsilateral DCIS if treated with radiation therapy (RT); (patients with synchronous or metachronous ipsilateral LCIS are eligible)
- History of non-breast malignancies, except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin, within 5 years prior to randomization
- Treatment including RT, chemotherapy, and/or targeted therapy for the currently diagnosed breast cancer prior to randomization
- Cardiac disease (history of and/or active disease) that would preclude the use of chemotherapy
- Pregnancy or lactation at the time of randomization; (Note: pregnancy testing must be performed within 2 weeks prior to randomization for women of childbearing potential)
- Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
- Use of any investigational product within 30 days prior to randomization
Trial Lead Organizations/Sponsors
Virginia Commonwealth University Massey Cancer CenterNational Cancer Institute
|Harry D. Bear||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01293032
ClinicalTrials.gov processed this data on December 02, 2014
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