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

Stage IIIA Breast Cancer Clinical Trial

Official title:

Choosing Neoadjuvant Chemotherapy Versus Hormonal Therapy for Breast Cancer Based on Gene Expression Profile

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01293032
• Other study ID #: MCC-13311
• Secondary ID: NCI-2010-02342P3
• Status: Active, not recruiting
• Phase: N/A
• First received: February 7, 2011
• Last updated: February 3, 2016
• Start date: April 2011
• Est. completion date: May 2016

Study information

• Verified date: February 2016
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: DNA analysis of tumor tissue may help doctors predict how well patients will respond to treatment and plan effective treatment.

PURPOSE: This pilot study is studying how well hormone therapy or chemotherapy before surgery based on gene expression analysis works in treating patients with breast cancer. The purpose of this research study is threefold. First, it is to determine if this approach to treatment is acceptable to participants. Second, it is to determine whether it is feasible to use the genetic make-up of your breast cancer cells to predict whether your disease will best respond to chemotherapy or hormonal therapy when given prior to surgery. Third, which is optional, is to determine if the blood levels of Insulin-like growth factor binding protein-2 IGFBP-2 can be used to monitor the response of your breast cancer to the treatment that you receive.

Description:

OBJECTIVES:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: May 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 if Cytokine-inducible SH2-containing protein (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

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 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 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 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal, Breast
• Carcinoma, Intraductal, Noninfiltrating
• Carcinoma, Lobular
• Ductal Breast Carcinoma in Situ
• Lobular Breast Carcinoma in Situ
• Stage II Breast Cancer
• Stage IIIA Breast Cancer
• Stage IIIB Breast Cancer

Intervention

Procedure:
• neoadjuvant therapy
Undergo neoadjuvant therapy
• therapeutic conventional surgery
Undergo therapeutic conventional surgery

Other:
• laboratory biomarker analysis
Correlative studies
• enzyme-linked immunosorbent assay
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
• tamoxifen citrate
Undergo hormonal therapy
• aromatase inhibition therapy
Undergo hormonal therapy

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal , Hôtel-Dieu Hospital	Montreal	Quebec
United States	Carolina Medical Center	Charlotte	North Carolina
United States	Forsyth Regional Cancer Center	Charlotte	North Carolina
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Methodist Cancer Center	Houston	Texas
United States	Lynchburg Hematology Oncology Clinic, Inc	Lynchburg	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington Cancer Institute	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Proportion of Patients With RS 11-25 Who Refuse the Assigned Treatment. Description.	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 Recurrence Score (RS), 11-25 scores, refuse the assigned treatment, randomized between hormonal and chemotherapy. The confidence interval will be 95%.	Up to 2 years	No

External Links

•   VCU Massey Cancer Center