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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00194792
Recruitment Status : Terminated
First Posted : September 19, 2005
Results First Posted : June 6, 2017
Last Update Posted : July 11, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Hannah Linden, University of Washington

Tracking Information
First Submitted Date  ICMJE September 14, 2005
First Posted Date  ICMJE September 19, 2005
Results First Submitted Date  ICMJE April 14, 2017
Results First Posted Date  ICMJE June 6, 2017
Last Update Posted Date July 11, 2017
Study Start Date  ICMJE August 2005
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
  • 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.
  • 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.
  • Disease-free Survival [ Time Frame: Up to 5 years ]
    Kaplan-Meier estimate assessed at 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.
  • 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
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
Pathologic response rate
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
Correlation of Molecular Markers With Response, Time to Progression, and Survival [ Time Frame: Weekly during CHB and XMN and pacitaxel ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
  • Clinical response rate following complete hormonal blockade.
  • Clinical response rate following chemotherapy.
  • Toxicity associated with these regimens.
  • Relapse rate.
  • Overall survival
  • Disease-free survival
  • Assessing whether the phenotype of breast cancer changes with treatment.
  • Assessing whether phenotypic changes in breast tumors predict outcome.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer
Official Title  ICMJE Neoadjuvant Complete Hormonal Blockade Followed by Neoadjuvant Chemotherapy for Resectable Hormone Receptor Positive, HER-2/Neu Negative Breast Cancer, A Phase II Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: exemestane
    Given PO
    Other Names:
    • Aromasin
    • FCE-24304
    • PNU 155971
  • Drug: triptorelin pamoate
    Given IM
    Other Names:
    • Pamorelin
    • Trelstar Depot
  • Drug: capecitabine
    Given PO
    Other Names:
    • CAPE
    • Ro 09-1978/000
    • Xeloda
  • Drug: methotrexate
    Given IV
    Other Names:
    • amethopterin
    • Folex
    • methylaminopterin
    • Mexate
    • MTX
  • Drug: vinorelbine tartrate
    Given IV
    Other Names:
    • Eunades
    • navelbine ditartrate
    • NVB
    • VNB
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Procedure: therapeutic conventional surgery
    Undergo lumpectomy or mastectomy
  • Radiation: radiation therapy
    Undergo radiation therapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (hormone therapy and chemotherapy)
See detailed description
Interventions:
  • Drug: exemestane
  • Drug: triptorelin pamoate
  • Drug: capecitabine
  • Drug: methotrexate
  • Drug: vinorelbine tartrate
  • Drug: paclitaxel
  • Procedure: therapeutic conventional surgery
  • Radiation: radiation therapy
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 5, 2017)
28
Original Enrollment  ICMJE
 (submitted: September 14, 2005)
50
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00194792
Other Study ID Numbers  ICMJE 6277
NCI-2010-00549 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hannah Linden, University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Hannah Linden Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP