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Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer

Primary Purpose

Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
exemestane
triptorelin pamoate
capecitabine
methotrexate
vinorelbine tartrate
paclitaxel
therapeutic conventional surgery
radiation therapy
laboratory biomarker analysis
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Estrogen Receptor-positive Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (hormone therapy and chemotherapy)

Arm Description

See detailed description

Outcomes

Primary Outcome Measures

Number of Participants With Clinical Response
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
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.
Disease-free Survival
Kaplan-Meier estimate assessed at 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.
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
Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation
Count of patients with dose reduction, treatment interruption, or treatment discontinuation.

Secondary Outcome Measures

Correlation of Molecular Markers With Response, Time to Progression, and Survival

Full Information

First Posted
September 14, 2005
Last Updated
June 9, 2017
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00194792
Brief Title
Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer
Official Title
Neoadjuvant Complete Hormonal Blockade Followed by Neoadjuvant Chemotherapy for Resectable Hormone Receptor Positive, HER-2/Neu Negative Breast Cancer, A Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Terminated
Study Start Date
August 2005 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (hormone therapy and chemotherapy)
Arm Type
Experimental
Arm Description
See detailed description
Intervention Type
Drug
Intervention Name(s)
exemestane
Other Intervention Name(s)
Aromasin, FCE-24304, PNU 155971
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
triptorelin pamoate
Other Intervention Name(s)
Pamorelin, Trelstar Depot
Intervention Description
Given IM
Intervention Type
Drug
Intervention Name(s)
capecitabine
Other Intervention Name(s)
CAPE, Ro 09-1978/000, Xeloda
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
amethopterin, Folex, methylaminopterin, Mexate, MTX
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vinorelbine tartrate
Other Intervention Name(s)
Eunades, navelbine ditartrate, NVB, VNB
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, TAX, Taxol
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Undergo lumpectomy or mastectomy
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Number of Participants With Clinical Response
Description
Defined as a > 50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease.
Time Frame
1 month
Title
Number of Participants With Microscopic Pathologic Complete Response and Macroscopic Pathologic Complete Response
Description
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
Title
Disease-free Survival
Description
Kaplan-Meier estimate assessed at 5 years
Time Frame
Up to 5 years
Title
Overall Survival
Description
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
Title
Quantification of All Grade 2, 3, 4 Adverse Events or Fatal Toxicities
Description
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)
Title
Number of Participants With Dose Reduction, Treatment Interruption, or Treatment Discontinuation
Description
Count of patients with dose reduction, treatment interruption, or treatment discontinuation.
Time Frame
During adjuvant and neoadjuvant chemotherapy
Secondary Outcome Measure Information:
Title
Correlation of Molecular Markers With Response, Time to Progression, and Survival
Time Frame
Weekly during CHB and XMN and pacitaxel

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hannah Linden
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer

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