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Hormone Therapy Or Chemotherapy Before Surgery Based on Gene Expression Analysis in Treating Patients With Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01293032
First received: February 7, 2011
Last updated: June 1, 2016
Last verified: June 2016

February 7, 2011
June 1, 2016
April 2011
May 2015   (final data collection date for primary outcome measure)
The Proportion of Patients With RS 11-25 Who Refused the Assigned Treatment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
The primary purpose of this trial is to determine the feasibility of carrying out a large multi-center trial with a similar design. Feasibility, in terms of less than 1/3 of patients with intermediate (11-25) Recurrence Score (RS) who refused the assigned treatment (Group 2) or refused randomization between hormonal (Arm 1) or chemotherapy (Arm 2). The confidence interval will be 95%. The proportion (and 95% confidence interval) of patients with RS 11-25 who refuse the assigned treatment will be calculated.
  • Number of patients who refuse assigned therapy [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    If more than 1/3 of patients refuse assigned therapy, a larger study would either be deemed not feasible or would have to be designed with the assumption that this proportion of patients would refuse assigned treatment
  • Objective clinical response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Percentages of patients with objective tumor regression by RECIST criteria
  • Percentages of planned breast-conserving therapy completed successfully [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Determine whether the type of neoadjuvant therapy (hormonal versus cytotoxic chemotherapy) chose on the basis of gene expression profiling will facilitate planned breast-conserving therapy
  • Clinical Complete Response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Proportion of patients who have a clinical complete response
  • Pathologic Complete Response Rate in the breast [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    No residual invasive cancer in the surgical specimens of the breast primary in 30-40% of patients with high (> 25) recurrence scores
  • Pathologic Complete Response Rate in the breast and lymph nodes [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    No residual invasive cancer in the surgical specimens of the breast primary and regional lymph nodes in 30-40% of patients with high (> 25) recurrence scores receiving chemotherapy
  • Pathologic residual cancer burden (RCB) at surgery [ Time Frame: Up to 2 hours ] [ Designated as safety issue: No ]
    RCB in the surgical specimens of breast and regional lymph nodes after completion of neoadjuvant chemotherapy in patients with high (> 25) recurrence scores
Complete list of historical versions of study NCT01293032 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Hormone Therapy Or Chemotherapy Before Surgery Based on Gene Expression Analysis in Treating Patients With Breast Cancer
Choosing Neoadjuvant Chemotherapy Versus Hormonal Therapy for Breast Cancer Based on Gene Expression Profile
This randomized pilot clinical trial studied whether the Oncotype DX gene expression "Recurrence Score" (RS) would be useful for helping make a decision about which type of pre-operative treatment, hormone therapy or chemotherapy would be a better for patients with hormone responsive cancers that were not suitable for breast conserving surgery. The RS is currently used to predict the risk of distant recurrence and the benefit of the addition of chemotherapy to hormonal therapy in the adjuvant setting.

Assessed the feasibility of carrying out a large-scale multi-center trial in which recurrence score (RS) was used to select treatment type in the neoadjuvant setting. Whether patients with intermediate RS were willing to be randomized between hormonal and chemotherapy.

The treatment received was not experimental and considered standard treatment for the type of cancer the participants had. What was experimental included the way in which they were assigned to a type of treatment. The design of this study was used to help determine if RS can be used to predict which type of treatment women with breast cancer are most likely to benefit from.

OUTLINE: Patients are assigned to 1 of 3 groups based on RS following Oncotype Dx gene expression profiling.

  • GROUP 1 (RS < 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 2 (RS 11-25): Patients are randomized to 1 of 2 treatment arms:

    • ARM 1: Patients receive neoadjuvant hormonal therapy as in group I.
    • ARM 2: 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 3 (RS > 25): Patients receive neoadjuvant chemotherapy as in group 2 arm 2.

All patients undergo surgery and receive hormonal therapy for at least 5 years.

After completion of study treatment, patients are followed up periodically.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Ductal Breast Carcinoma in Situ
  • Lobular Breast Carcinoma in Situ
  • Stage II Breast Cancer
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Procedure: Neoadjuvant Therapy
    Undergo neoadjuvant therapy
    Other Names:
    • Induction Therapy
    • Neoadjuvant
    • Preoperative Therapy
  • Procedure: Therapeutic Conventional Surgery
    Undergo therapeutic conventional surgery
  • Other: Laboratory Biomarker Analysis
    Correlative studies
    Other Name: Correlative studies
  • Genetic: Gene Expression Analysis
    Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).
  • Drug: Systemic Chemotherapy
    Undergo chemotherapy
  • Drug: Tamoxifen Citrate
    Undergo hormonal therapy
    Other Names:
    • Nolvadex
    • TAM
    • tamoxifen
    • TMX
    • hormonal therapy
  • Drug: Aromatase Inhibition Therapy
    Undergo hormonal therapy
    Other Names:
    • Inhibition therapy, aromatase
    • Aromatase Inhibition
    • hormonal therapy
  • Experimental: Group 1 (RS < 11)

    Patients with a Recurrence Score (RS) less than 11 (RS <11) are assigned to Group 1, neoadjuvant hormonal therapy either tamoxifen (pre-menopausal women) or an aromatase inhibitor (post-menopausal women) for 4-6 months in the absence of disease progression or unacceptable toxicity.

    Treatment:

    • Neoadjuvant therapy
    • Therapeutic conventional surgery
    • Laboratory biomarker analysis/Correlative studies
    • Gene Expression Analysis/ Oncotype DX Gene Expression Profiling System
    • Hormonal therapy:

      • Tamoxifen Citrate (pre-menopausal women) OR
      • Aromatase Inhibition Therapy (post-menopausal women)
    Interventions:
    • Procedure: Neoadjuvant Therapy
    • Procedure: Therapeutic Conventional Surgery
    • Other: Laboratory Biomarker Analysis
    • Genetic: Gene Expression Analysis
    • Drug: Tamoxifen Citrate
    • Drug: Aromatase Inhibition Therapy
  • Experimental: Group 2 Arm 1 (RS 11-25)

    Patients with an intermediate RS (11-25) assigned to Group 2. Randomized to Arm 1, neoadjuvant hormonal therapy as in Group 1.

    Treatment:

    • Neoadjuvant therapy
    • Therapeutic conventional surgery
    • Laboratory biomarker analysis/Correlative studies
    • Gene Expression Analysis/ Oncotype DX Gene Expression Profiling System
    • Hormonal therapy:

      • Tamoxifen Citrate (pre-menopausal women) OR
      • Aromatase Inhibition Therapy (post-menopausal women)
    Interventions:
    • Procedure: Neoadjuvant Therapy
    • Procedure: Therapeutic Conventional Surgery
    • Other: Laboratory Biomarker Analysis
    • Genetic: Gene Expression Analysis
    • Drug: Tamoxifen Citrate
    • Drug: Aromatase Inhibition Therapy
  • Experimental: Group 2 Arm 2 (RS 11-25)

    Patients with an intermediate RS(11-25) assigned to Group 2. Randomized to Arm 2, neoadjuvant chemotherapy 6-8 courses of anthracycline/taxane based regimen over 4-6 months in the absence of disease progression or unacceptable toxicity.

    Treatment:

    • Neoadjuvant therapy
    • Therapeutic conventional surgery
    • Laboratory biomarker analysis/Correlative studies
    • Gene Expression Analysis/Oncotype DX Gene Expression Profiling System
    • Systemic chemotherapy
    Interventions:
    • Procedure: Neoadjuvant Therapy
    • Procedure: Therapeutic Conventional Surgery
    • Other: Laboratory Biomarker Analysis
    • Genetic: Gene Expression Analysis
    • Drug: Systemic Chemotherapy
  • Experimental: Group 3 (RS > 25)

    Patients with a high RS (> 25) assigned to Group 3, neoadjuvant chemotherapy as in Group 2 Arm 2.

    Treatment:

    • Neoadjuvant therapy
    • Therapeutic conventional surgery
    • Laboratory biomarker analysis/Correlative studies
    • Gene Expression Analysis/Oncotype DX Gene Expression Profiling System
    • Systemic chemotherapy
    Interventions:
    • Procedure: Neoadjuvant Therapy
    • Procedure: Therapeutic Conventional Surgery
    • Other: Laboratory Biomarker Analysis
    • Genetic: Gene Expression Analysis
    • Drug: Systemic Chemotherapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
59
March 2016
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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 institutional review board (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 Eastern Cooperative Oncology Group Score (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 Chromosome 17 centromere (CEP17) must be < 2.2) or, if a ratio was not performed, the HER2 gene copy number must be < 4 per nucleus; or
    • Chromogenic in situ hybridization (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 have been evaluated by a treating physician, reviewed and discussed by the multi-disciplinary breast team, and considered to be a candidate for chemotherapy

Exclusion Criteria:

  • 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 registration
  • 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 ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (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 registration
  • 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 registration
Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01293032
MCC-13311, NCI-2010-02342, P30CA016059
Yes
Yes
Not Provided
Virginia Commonwealth University
Virginia Commonwealth University
National Cancer Institute (NCI)
Principal Investigator: Harry D. Bear, MD, PhD Virginia Commonwealth University
Virginia Commonwealth University
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP