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

NCT01293032 | Completed Results DMC

• 3 other identifiers: MCC-13311NCI-2010-02342P30CA016059
• Study Type: interventional
• Target: 59
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

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

Keywords

Estrogen Receptor Positive; Progesterone Receptor Positive; HER2/Neu Negative; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• The Proportion of Patients With RS 11-25 Who Refused the Assigned Treatment

  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.

  Up to 2 years

Study Arms (4)

Group 1 (RS < 11)

EXPERIMENTAL

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; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis; Genetic: Gene Expression Analysis; Drug: Tamoxifen Citrate; Drug: Aromatase Inhibition Therapy

Group 2 Arm 1 (RS 11-25)

EXPERIMENTAL

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; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis; Genetic: Gene Expression Analysis; Drug: Tamoxifen Citrate; Drug: Aromatase Inhibition Therapy

Group 2 Arm 2 (RS 11-25)

EXPERIMENTAL

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; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis; Genetic: Gene Expression Analysis; Drug: Systemic Chemotherapy

Group 3 (RS > 25)

EXPERIMENTAL

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; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis; Genetic: Gene Expression Analysis; Drug: Systemic Chemotherapy

Interventions

Neoadjuvant Therapy PROCEDURE

Undergo neoadjuvant therapy

Also known as: Induction Therapy, Neoadjuvant, Preoperative Therapy

Group 1 (RS < 11); Group 2 Arm 1 (RS 11-25); Group 2 Arm 2 (RS 11-25); Group 3 (RS > 25)

Therapeutic Conventional Surgery PROCEDURE

Undergo therapeutic conventional surgery

Group 1 (RS < 11); Group 2 Arm 1 (RS 11-25); Group 2 Arm 2 (RS 11-25); Group 3 (RS > 25)

Laboratory Biomarker Analysis OTHER

Correlative studies

Also known as: Correlative studies

Group 1 (RS < 11); Group 2 Arm 1 (RS 11-25); Group 2 Arm 2 (RS 11-25); Group 3 (RS > 25)

Gene Expression Analysis GENETIC

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

Group 1 (RS < 11); Group 2 Arm 1 (RS 11-25); Group 2 Arm 2 (RS 11-25); Group 3 (RS > 25)

Systemic Chemotherapy DRUG

Undergo chemotherapy

Group 2 Arm 2 (RS 11-25); Group 3 (RS > 25)

Tamoxifen Citrate DRUG

Undergo hormonal therapy

Also known as: Nolvadex, TAM, tamoxifen, TMX, hormonal therapy

Group 1 (RS < 11); Group 2 Arm 1 (RS 11-25)

Aromatase Inhibition Therapy DRUG

Undergo hormonal therapy

Also known as: Inhibition therapy, aromatase, Aromatase Inhibition, hormonal therapy

Group 1 (RS < 11); Group 2 Arm 1 (RS 11-25)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Washington Cancer Institute

Washington D.C., District of Columbia, 20010, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Forsyth Regional Cancer Center

Charlotte, North Carolina, 28204, United States

Location

Cone Health Cancer Center

Greensboro, North Carolina, 27403, United States

Location

Methodist Cancer Center

Houston, Texas, 77030, United States

Location

Lynchburg Hematology Oncology Clinic, Inc

Lynchburg, Virginia, 24501, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

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

Montreal, Quebec, H2W 1T8, Canada

Location

Related Links

• VCU Massey Cancer Center

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ; Breast Neoplasms

Interventions

Neoadjuvant Therapy; Gene Expression Profiling; Tamoxifen; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Genetic Techniques; Investigative Techniques; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Results Point of Contact

• Title: Harry D Bear, MD, PhD
• Organization: Virginia Commonwealth University/Massey Cancer Center

harry.bear@vcuhealth.org

804-828-9325

Study Officials

• Harry D. Bear, MD, PhD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2011
• First Posted: February 10, 2011
• Study Start: April 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: March 1, 2016
• Last Updated: July 12, 2016
• Results First Posted: July 12, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (7)