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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00549 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (hormone therapy and chemotherapy) | Experimental | See detailed description |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| exemestane | Drug | Given PO |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinical Response | Defined as a > 50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease. | 1 month |
| 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. | From date of treatment start to surgery |
| Disease-free Survival | Kaplan-Meier estimate assessed at 5 years | Up to 5 years |
| 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. | Up to 5 years |
| 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 | Monthly during neoadjuvant treatment and then 6 months following treatment (including surgery) |
| Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation | Count of patients with dose reduction, treatment interruption, or treatment discontinuation. | During adjuvant and neoadjuvant chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of Molecular Markers With Response, Time to Progression, and Survival | Weekly during CHB and XMN and pacitaxel |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hannah Linden | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| triptorelin pamoate | Drug | Given IM |
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| capecitabine | Drug | Given PO |
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| methotrexate | Drug | Given IV |
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| vinorelbine tartrate | Drug | Given IV |
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| paclitaxel | Drug | Given IV |
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| therapeutic conventional surgery | Procedure | Undergo lumpectomy or mastectomy |
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| radiation therapy | Radiation | Undergo radiation therapy |
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| laboratory biomarker analysis | Other | Correlative studies |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | 1 month |
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| 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. | Posted | Count of Participants | Participants | From date of treatment start to surgery |
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| Primary | Disease-free Survival | Kaplan-Meier estimate assessed at 5 years | Posted | Number | 95% Confidence Interval | disease free survival probability | Up to 5 years |
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| 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. | Posted | Number | 95% Confidence Interval | survival probability | Up to 5 years |
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| 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 | Posted | Number | events | Monthly during neoadjuvant treatment and then 6 months following treatment (including surgery) |
|
| ||||||||||||||||||||||||||||
| Primary | Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation | Count of patients with dose reduction, treatment interruption, or treatment discontinuation. | Posted | Count of Participants | Participants | During adjuvant and neoadjuvant chemotherapy |
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| Secondary | Correlation of Molecular Markers With Response, Time to Progression, and Survival | Molecular marker data was not collected for this cohort and thus not possible to report results for this outcome. | Posted | Weekly during CHB and XMN and pacitaxel |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 0 | 27 | 23 | 27 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| High Blood Pressure | Vascular disorders |
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| Fatigue | General disorders |
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| Nausea | Gastrointestinal disorders |
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| Dysgeusia | Gastrointestinal disorders |
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| Fever | General disorders |
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| SGOT Increased | Investigations |
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| SGPT Increased | Investigations |
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| Albumin Decreased | Investigations |
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| Potassium Decreased | Investigations |
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| Anxiety | Psychiatric disorders |
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| Diarrhea | Gastrointestinal disorders |
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| Alopecia | Skin and subcutaneous tissue disorders |
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| Mucositis (GI) | Gastrointestinal disorders |
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| Mucositis (Oral) | Gastrointestinal disorders |
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| Neutrophil Count Decreased | Investigations |
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| Alkaline Phosphatase Increased | Investigations |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders |
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| Insomnia | Psychiatric disorders |
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| Heartburn | Gastrointestinal disorders |
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| Hemoglobin Decreased | Investigations |
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| White Blood Cells Decreased | Investigations |
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| Depression | Psychiatric disorders |
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| Pain (arm) | General disorders |
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| Hot Flashes/Night Sweats | Vascular disorders |
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| Pain (neck & jaw) | General disorders |
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| Pain (back) | General disorders |
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| Constipation | Gastrointestinal disorders |
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| Headache | Nervous system disorders |
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| Pain (subcostal) | General disorders |
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| Pain (abdominal) | Gastrointestinal disorders |
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| Dry Skin (hands) | Skin and subcutaneous tissue disorders |
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| Hematocrit Decreased | Investigations |
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| Hypocalcemia | Investigations |
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| Joint Pain/Muscle Aches | General disorders |
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| Amenorrhea | Reproductive system and breast disorders |
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| GI Upset/Reflux | Gastrointestinal disorders |
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| Sodium Decreased | Investigations |
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| Hand Foot Syndrome | Skin and subcutaneous tissue disorders |
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| Common Cold | Respiratory, thoracic and mediastinal disorders |
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| Vomiting | Gastrointestinal disorders |
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| Rash (Eczema) | Skin and subcutaneous tissue disorders |
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| Lactate Dehydrogenase Increased | Investigations |
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| Glucose Increased | Investigations |
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| Pain (bone) | Musculoskeletal and connective tissue disorders |
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| Yeast Infection (vaginal) | Reproductive system and breast disorders |
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| Dry Skin | Skin and subcutaneous tissue disorders |
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| SOB with activity | Respiratory, thoracic and mediastinal disorders |
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| UTI | Renal and urinary disorders |
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| Hyperpigmentation (lymphs) | Skin and subcutaneous tissue disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Hannah Linden | University of Washington / Seattle Cancer Care Alliance | 206-288-6989 | hmlinden@uw.edu |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C056516 | exemestane |
| D017329 | Triptorelin Pamoate |
| D000069287 | Capecitabine |
| D008727 | Methotrexate |
| C015342 | merphos |
| D000077235 | Vinorelbine |
| D017239 | Paclitaxel |
| D013660 | Taxes |
| D011878 | Radiotherapy |
| D011827 | Radiation |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
| D013812 | Therapeutics |
| D055585 | Physical Phenomena |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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