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

NCT ID: NCT01293032

Last Updated: 2016-07-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-04-30

Study Completion Date

2016-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

Neoadjuvant Therapy

Intervention Type PROCEDURE

Undergo neoadjuvant therapy

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo therapeutic conventional surgery

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Gene Expression Analysis

Intervention Type GENETIC

Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).

Tamoxifen Citrate

Intervention Type DRUG

Undergo hormonal therapy

Aromatase Inhibition Therapy

Intervention Type DRUG

Undergo hormonal therapy

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)

Group Type EXPERIMENTAL

Neoadjuvant Therapy

Intervention Type PROCEDURE

Undergo neoadjuvant therapy

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo therapeutic conventional surgery

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Gene Expression Analysis

Intervention Type GENETIC

Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).

Tamoxifen Citrate

Intervention Type DRUG

Undergo hormonal therapy

Aromatase Inhibition Therapy

Intervention Type DRUG

Undergo hormonal therapy

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

Group Type EXPERIMENTAL

Neoadjuvant Therapy

Intervention Type PROCEDURE

Undergo neoadjuvant therapy

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo therapeutic conventional surgery

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Gene Expression Analysis

Intervention Type GENETIC

Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).

Systemic Chemotherapy

Intervention Type DRUG

Undergo chemotherapy

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

Group Type EXPERIMENTAL

Neoadjuvant Therapy

Intervention Type PROCEDURE

Undergo neoadjuvant therapy

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo therapeutic conventional surgery

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Gene Expression Analysis

Intervention Type GENETIC

Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).

Systemic Chemotherapy

Intervention Type DRUG

Undergo chemotherapy

Interventions

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Neoadjuvant Therapy

Undergo neoadjuvant therapy

Intervention Type PROCEDURE

Therapeutic Conventional Surgery

Undergo therapeutic conventional surgery

Intervention Type PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

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).

Intervention Type GENETIC

Systemic Chemotherapy

Undergo chemotherapy

Intervention Type DRUG

Tamoxifen Citrate

Undergo hormonal therapy

Intervention Type DRUG

Aromatase Inhibition Therapy

Undergo hormonal therapy

Intervention Type DRUG

Other Intervention Names

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Induction Therapy Neoadjuvant Preoperative Therapy Correlative studies Nolvadex TAM tamoxifen TMX hormonal therapy Inhibition therapy, aromatase Aromatase Inhibition hormonal therapy

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Virginia Commonwealth University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Harry D. Bear, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

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Washington Cancer Institute

Washington D.C., District of Columbia, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Forsyth Regional Cancer Center

Charlotte, North Carolina, United States

Site Status

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status

Methodist Cancer Center

Houston, Texas, United States

Site Status

Lynchburg Hematology Oncology Clinic, Inc

Lynchburg, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Centre Hospitalier de l'Université de Montréal , Hôtel-Dieu Hospital

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Related Links

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http://www.massey.vcu.edu/

VCU Massey Cancer Center

Other Identifiers

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NCI-2010-02342

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA016059

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MCC-13311

Identifier Type: -

Identifier Source: org_study_id

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