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

This study is ongoing, but not recruiting participants.
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: February 3, 2016
Last verified: February 2016

February 7, 2011
February 3, 2016
April 2011
May 2015   (final data collection date for primary outcome measure)
The Proportion of Patients With RS 11-25 Who Refuse the Assigned Treatment. Description. [ 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 Recurrence Score (RS), 11-25 scores, refuse the assigned treatment, randomized between hormonal and chemotherapy. The confidence interval will be 95%.
  • 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

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.

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.

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 IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Procedure: neoadjuvant therapy
    Undergo neoadjuvant therapy
  • Procedure: therapeutic conventional surgery
    Undergo therapeutic conventional surgery
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: enzyme-linked immunosorbent assay
    Correlative studies
    Other Name: ELISA
  • 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
  • Drug: aromatase inhibition therapy
    Undergo hormonal therapy
    Other Name: inhibition therapy, aromatase
  • Experimental: GROUP I (RS < 11)
    Patients who receive a recurrence score of less than 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.
    Interventions:
    • Procedure: neoadjuvant therapy
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
    • Other: enzyme-linked immunosorbent assay
    • Genetic: gene expression analysis
    • Drug: tamoxifen citrate
    • Drug: aromatase inhibition therapy
  • Experimental: GROUP II ARM I (RS 11-25)
    Patients with an intermediate score (11-25) will be randomized to receive neoadjuvant hormonal therapy as in group I.
    Interventions:
    • Procedure: neoadjuvant therapy
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
    • Other: enzyme-linked immunosorbent assay
    • Genetic: gene expression analysis
    • Drug: tamoxifen citrate
    • Drug: aromatase inhibition therapy
  • Experimental: GROUP II ARM II (RS 11-25)
    Patients with an intermediate score (11-25) will be randomized to 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.
    Interventions:
    • Procedure: neoadjuvant therapy
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
    • Other: enzyme-linked immunosorbent assay
    • Genetic: gene expression analysis
    • Drug: systemic chemotherapy
  • Experimental: GROUP III (RS > 25)
    Patients with RS high scores (> 25) will receive chemotherapy. Patients receive neoadjuvant chemotherapy as in arm II of group II.
    Interventions:
    • Procedure: neoadjuvant therapy
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
    • Other: enzyme-linked immunosorbent assay
    • 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.
 
Active, not recruiting
64
May 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 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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01293032
MCC-13311, NCI-2010-02342, P30CA016059
Yes
Not Provided
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
February 2016

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