CompletedNCT01293032Updated Jul 12, 2016Results posted

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

An interventional study of Neoadjuvant Therapy and Therapeutic Conventional Surgery in Ductal Breast Carcinoma in Situ, Lobular Breast Carcinoma in Situ and Stage II Breast Cancer, sponsored by Virginia Commonwealth University. Completed at 8 sites in 2 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-07-12.

Sponsored by Virginia Commonwealth University · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 59
Allocation: Randomized
Ages: 18 Years and older
Sex: Female

Study 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.

Read the 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.

Conditions studied

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

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Keywords

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

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 59 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.

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Lead sponsor

Virginia Commonwealth University is the lead sponsor of 641 studies on the registry; 82 are open to participants now.

Of its 88 completed or terminated interventional studies of FDA-regulated products, 62 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

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

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

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 59 participants (actual)

Study arms

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

Interventions

ProcedureNeoadjuvant Therapy
Undergo neoadjuvant therapy
Also known as: Induction Therapy, Neoadjuvant, Preoperative Therapy
ProcedureTherapeutic Conventional Surgery
Undergo therapeutic conventional surgery
OtherLaboratory Biomarker Analysis
Correlative studies
Also known as: Correlative studies
GeneticGene Expression Analysis
Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).
DrugSystemic Chemotherapy
Undergo chemotherapy
DrugTamoxifen Citrate
Undergo hormonal therapy
Also known as: Nolvadex, TAM, tamoxifen, TMX, hormonal therapy
DrugAromatase Inhibition Therapy
Undergo hormonal therapy
Also known as: Inhibition therapy, aromatase, Aromatase Inhibition, hormonal therapy

What researchers measure

Primary outcomes

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.
Time frame: Up to 2 years

Results

Posted Jul 12, 2016

Participant flow

Once a patient consented to this study and was deemed eligible the core biopsy blocks or slides were sent to obtain the Oncotype DX Breast Cancer Assay. After the Recurrence Score(RS) results were available the subject was assigned to Group 1, 2, or 3. If assigned to Group 2 they were randomized to Arm 1 or Arm 2.

Recurrence Score(RS)Assigned/Randomized

Participant flow — Recurrence Score(RS)Assigned/Randomized
Milestone	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)
Started	12	17	16	14
Assigned/randomized to arm	12	17	16	14
Completed	12	17	11	14
Not completed	0	0	5	0
Withdrew: Refused assigned arm	0	0	5	0

Treatment

Participant flow — Treatment
Milestone	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)
Started	12	19	11	14
Completed	10	14	10	13
Not completed	2	5	1	1
Withdrew: Adverse event	0	0	1	1
Withdrew: Withdrawal by subject	2	4	0	0
Withdrew: Disease progression, relapse	0	1	0	0

Outcome measures

PrimaryThe 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.

Time frame:: Up to 2 years
Reported as:: Number · proportion of participants

The Proportion of Patients With RS 11-25 Who Refused the Assigned Treatment
proportion of participants	Group 2 (RS 11-25)
The Proportion of Patients With RS 11-25 Who Refused the Assigned Treatment	0.15 (0.051 to 0.319)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Group 1 (RS < 11)	—	—	—
Group 2 Arm 1 (RS 11-25)	—	—	—
Group 2 Arm 2 (RS 11-25)	—	—	—
Group 3 (RS > 25)	—	—	—

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)	Total
<=18 years	0	0	0	0	0
Between 18 and 65 years	5	8	13	10	36
>=65 years	7	9	3	4	23

Age, Continuous
Age, Continuous(years)	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)	Total
Mean	55.3125 ± 5.931426	63.64706 ± 11.5539	55.3125 ± 12.2556	60.64286 ± 7.312867	61.25423729 ± 10.52188724

Sex: Female, Male
Sex: Female, Male(Participants)	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)	Total
Female	12	17	16	14	59
Male	0	0	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)	Total
Hispanic or Latino	1	0	1	0	2
Not Hispanic or Latino	11	16	15	14	56
Unknown or Not Reported	0	1	0	0	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	5	0	4	2	11
White	7	17	12	12	48
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Group 1 (RS < 11)	Group 2 Arm 1 (RS 11-25)	Group 2 Arm 2 (RS 11-25)	Group 3 (RS > 25)	Total
Canada	1	4	2	4	11
United States	11	13	14	10	48

Study locations

8 sites

Washington Cancer Institute
Washington, District of Columbia 20010, United States
Carolinas Medical Center
Charlotte, North Carolina 28203, United States
Forsyth Regional Cancer Center
Charlotte, North Carolina 28204, United States
Cone Health Cancer Center
Greensboro, North Carolina 27403, United States
Methodist Cancer Center
Houston, Texas 77030, United States
Lynchburg Hematology Oncology Clinic, Inc
Lynchburg, Virginia 24501, United States
Virginia Commonwealth University
Richmond, Virginia 23298, United States
Centre Hospitalier de l'Université de Montréal , Hôtel-Dieu Hospital
Montreal, Quebec H2W 1T8, Canada

References and documents

Individual participant data

Plan to share: Yes

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 12, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01293032
Lead sponsor: Virginia Commonwealth University
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Feb 10, 2011
Start date: Apr 2011
Primary completion: May 2015
Completion: Mar 2016
Results posted: Jul 12, 2016
Last update: Jul 12, 2016

Study contacts

Harry D. Bear, MD, PhD

principal investigator · Virginia Commonwealth University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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