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
  Purpose
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.

Condition Intervention
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
Procedure: Therapeutic Conventional Surgery
Other: Laboratory Biomarker Analysis
Genetic: Gene Expression Analysis
Drug: Systemic Chemotherapy
Drug: Tamoxifen Citrate
Drug: Aromatase Inhibition Therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Choosing Neoadjuvant Chemotherapy Versus Hormonal Therapy for Breast Cancer Based on Gene Expression Profile

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • 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.


Enrollment: 59
Study Start Date: April 2011
Study Completion Date: March 2016
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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: 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 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)
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: 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 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
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
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
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01293032

Locations
United States, District of Columbia
Washington Cancer Institute
Washington, District of Columbia, United States, 20010
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Forsyth Regional Cancer Center
Charlotte, North Carolina, United States, 28204
Cone Health Cancer Center
Greensboro, North Carolina, United States, 27403
United States, Texas
Methodist Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Lynchburg Hematology Oncology Clinic, Inc
Lynchburg, Virginia, United States, 24501
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Canada, Quebec
Centre Hospitalier de l'Université de Montréal , Hôtel-Dieu Hospital
Montreal, Quebec, Canada, H2W 1T8
Sponsors and Collaborators
Virginia Commonwealth University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Harry D. Bear, MD, PhD Virginia Commonwealth University
  More Information

Additional Information:
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01293032     History of Changes
Other Study ID Numbers: MCC-13311  NCI-2010-02342  P30CA016059 
Study First Received: February 7, 2011
Results First Received: April 5, 2016
Last Updated: June 1, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes

Keywords provided by Virginia Commonwealth University:
Estrogen Receptor Positive
Progesterone Receptor Positive
HER2/Neu Negative
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Ductal, Breast
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Lobular
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Ductal
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Tamoxifen
Citric Acid
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents

ClinicalTrials.gov processed this record on July 28, 2016