Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
Conditions
Brief summary
This phase II trial is studying how well giving hormone therapy together with combination chemotherapy before and after surgery works in treating patients with stage I-IIIA breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane and triptorelin pamoate may fight breast cancer by lowering the amount of estrogen the body makes. Drugs used in chemotherapy, such as capecitabine, methotrexate, vinorelbine ditartrate, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving hormone therapy together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery
Detailed description
PRIMARY OBJECTIVES: I. To assess the pathologic response rate in patients with operable breast cancer treated with a two part, neoadjuvant regimen consisting of complete hormonal blockade (CHB) for 2 weeks followed by four three-week cycles of Xeloda, Methotrexate and Navelbine with continuation of complete hormonal blockade. SECONDARY OBJECTIVES: I. To assess the clinical response rate in patients with surgically resectable breast cancer treated with complete hormonal blockade and four three-week cycles of Xeloda, Methotrexate and Navelbine. II. To assess the toxicity associated with these regimens. III. To assess the relapse rate, overall and disease-free survival in patients with operable breast cancer when treated with neoadjuvant CHB and XMN + CHB followed by adjuvant treatment using XMN or Taxol. IV. To assess whether the phenotype of breast cancer changes with treatment. V. To assess whether phenotypic changes in breast tumors predict outcome. OUTLINE: NEOADJUVANT CHB: Patients receive exemestane orally (PO) daily for 14 weeks. Premenopausal patients also receive triptorelin pamoate intramuscularly (IM) once monthly for 4 months beginning 2 weeks before the initiation of exemestane. NEOADJUVANT CHEMOTHERAPY: Patients receive capecitabine PO twice daily (BID) on days 1-14 and methotrexate intravenously (IV) and vinorelbine ditartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses. SURGERY: Patients then undergo definitive surgical resection with or without radiation therapy. ADJUVANT CHEMOTHERAPY: Patients with microscopic complete response (pCR) or disease that has been down-staged to =\< 1 cm with no positive nodes receive capecitabine PO BID on days 1-14 and methotrexate IV and vinorelbine ditartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses. Patients with down-staged T and 0 or 1 positive node receive paclitaxel IV over 1 hour once weekly for 12 weeks. ADJUVANT HORMONAL THERAPY: Patients receive hormonal therapy for 5 years. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Interventions
DRUGexemestane
Given PO
Given IM
DRUGcapecitabine
Given PO
DRUGmethotrexate
Given IV
DRUGvinorelbine tartrate
Given IV
DRUGpaclitaxel
Given IV
PROCEDUREtherapeutic conventional surgery
Undergo lumpectomy or mastectomy
RADIATIONradiation therapy
Undergo radiation therapy
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically confirmed, operable ER or PR +, HER2/neu negative, radiographically measurable breast cancer \> 1cm (Operable lesions are T1c - T3 and N0 - N2a; histologic confirmation should be by core needle biopsy only) * Be chemotherapy naive * Have an ECOG performance status of =\< 2 * Be assessed for menopausal status (For study purposes, postmenopausal is defined as: a prior documented bilateral oophorectomy, or a history of at least 12 months without spontaneous menstrual bleeding, or age 60 or older with a prior hysterectomy without oophorectomy, or Age less than 60 with a prior hysterectomy without oophorectomy \[or in whom the status of the ovaries is unknown\], with a documented FSH level demonstrating confirmatory elevation in the postmenopausal range for the lab) * All premenopausal patients must have a baseline FSH and LH * ANC \>= 1,500 * Platelet count \>= 100,000 * Serum creatinine =\< 1.5 x IULN * Estimated creatinine clearance \> 50 ml/min * Have staging studies and tumor assessment prior to registration * Bone density exam must be done within the first 3 months of complete hormonal blockade * Have a negative pregnancy test within seven days prior to registration if of childbearing potential * Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures
Exclusion criteria
* Primary tumor =\< 1 cm, not measurable; inflammatory disease * Pregnant or lactating; women of childbearing potential with either a positive or no pregnancy test at baseline are excluded (Women of childbearing potential who are not using a reliable and appropriate contraceptive method are excluded; patients must agree to continue contraception for 30 days from the last study drug administration) * Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil * Previous enrollment in an investigational drug study within the last 4 weeks * Evidence of distant metastatic disease * Prior chemotherapy or hormonal therapy for breast cancer * Prior malignancy other than adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, other stage I or II cancer from which the patient has been disease free for at least 5 years * History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance with oral drug intake * Any other life-threatening illness (e.g. serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication or myocardial infarction * Major surgery within four weeks of the start of study treatment without complete recovery * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome * Known, existing uncontrolled coagulopathy * Unwillingness to give informed consent * Unwillingness to participate or inability to comply with the protocol for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival | Up to 5 years | Kaplan-Meier estimate assessed at 5 years |
| Number of Participants With Clinical Response | 1 month | Defined as a \> 50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease. |
| Number of Participants With Microscopic Pathologic Complete Response and Macroscopic Pathologic Complete Response | From date of treatment start to surgery | Defined as no evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection and the examining pathologist cannot identify gross residual tumor mass in the surgical specimen. |
| Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation | During adjuvant and neoadjuvant chemotherapy | Count of patients with dose reduction, treatment interruption, or treatment discontinuation. |
| Overall Survival | Up to 5 years | From the start of protocol therapy until the date of death from any cause or the last date the patient was known to be alive. Kaplan-Meier estimate assessed at 5 years. |
| Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities | Monthly during neoadjuvant treatment and then 6 months following treatment (including surgery) | Count of all incidences of grade 2, 3, 4 adverse events and fatal toxicities |
Secondary
| Measure | Time frame |
|---|---|
| Correlation of Molecular Markers With Response, Time to Progression, and Survival | Weekly during CHB and XMN and pacitaxel |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Hormone Therapy and Chemotherapy) See detailed description
exemestane: Given PO
triptorelin pamoate: Given IM
capecitabine: Given PO
methotrexate: Given IV
vinorelbine tartrate: Given IV
paclitaxel: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
radiation therapy: Undergo radiation therapy
laboratory biomarker analysis: Correlative studies | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Hormone Therapy and Chemotherapy) |
|---|---|
| Age, Continuous | 55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Disease-free Survival
Kaplan-Meier estimate assessed at 5 years
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Hormone Therapy and Chemotherapy) | Disease-free Survival | 0.76 disease free survival probability |
Primary
Number of Participants With Clinical Response
Defined as a \> 50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease.
Time frame: 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Hormone Therapy and Chemotherapy) | Number of Participants With Clinical Response | 19 Participants |
Primary
Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation
Count of patients with dose reduction, treatment interruption, or treatment discontinuation.
Time frame: During adjuvant and neoadjuvant chemotherapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Hormone Therapy and Chemotherapy) | Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation | Adjuvant therapy | 1 Participants |
| Treatment (Hormone Therapy and Chemotherapy) | Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation | Neoadjuvant therapy | 11 Participants |
Primary
Number of Participants With Microscopic Pathologic Complete Response and Macroscopic Pathologic Complete Response
Defined as no evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection and the examining pathologist cannot identify gross residual tumor mass in the surgical specimen.
Time frame: From date of treatment start to surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Hormone Therapy and Chemotherapy) | Number of Participants With Microscopic Pathologic Complete Response and Macroscopic Pathologic Complete Response | 0 Participants |
Primary
Overall Survival
From the start of protocol therapy until the date of death from any cause or the last date the patient was known to be alive. Kaplan-Meier estimate assessed at 5 years.
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Hormone Therapy and Chemotherapy) | Overall Survival | 0.88 survival probability |
Primary
Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities
Count of all incidences of grade 2, 3, 4 adverse events and fatal toxicities
Time frame: Monthly during neoadjuvant treatment and then 6 months following treatment (including surgery)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Hormone Therapy and Chemotherapy) | Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities | Grade 2 | 80 events |
| Treatment (Hormone Therapy and Chemotherapy) | Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities | Grade 3 | 12 events |
| Treatment (Hormone Therapy and Chemotherapy) | Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities | Grade 4 | 0 events |
| Treatment (Hormone Therapy and Chemotherapy) | Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities | Fatal toxicity | 0 events |
Secondary
Correlation of Molecular Markers With Response, Time to Progression, and Survival
Time frame: Weekly during CHB and XMN and pacitaxel
Population: Molecular marker data was not collected for this cohort and thus not possible to report results for this outcome.