- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00194792
Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer
Neoadjuvant Complete Hormonal Blockade Followed by Neoadjuvant Chemotherapy for Resectable Hormone Receptor Positive, HER-2/Neu Negative Breast Cancer, A Phase II Study
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (hormone therapy and chemotherapy)
See detailed description
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Undergo radiation therapy
Other Names:
Undergo lumpectomy or mastectomy
Given PO
Other Names:
Given IM
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Clinical Response
Time Frame: 1 month
|
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
Time Frame: 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.
|
From date of treatment start to surgery
|
Disease-free Survival
Time Frame: Up to 5 years
|
Kaplan-Meier estimate assessed at 5 years
|
Up to 5 years
|
Overall Survival
Time Frame: 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.
|
Up to 5 years
|
Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities
Time Frame: 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
|
Monthly during neoadjuvant treatment and then 6 months following treatment (including surgery)
|
Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation
Time Frame: During adjuvant and neoadjuvant chemotherapy
|
Count of patients with dose reduction, treatment interruption, or treatment discontinuation.
|
During adjuvant and neoadjuvant chemotherapy
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Correlation of Molecular Markers With Response, Time to Progression, and Survival
Time Frame: Weekly during CHB and XMN and pacitaxel
|
Weekly during CHB and XMN and pacitaxel
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Phytogenic
- Dermatologic Agents
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptive Agents, Female
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Luteolytic Agents
- Paclitaxel
- Capecitabine
- Vinorelbine
- Methotrexate
- Triptorelin Pamoate
- Exemestane
Other Study ID Numbers
- 6277
- NCI-2010-00549 (REGISTRY: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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