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

This study has been terminated.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00194792
First received: September 14, 2005
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
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
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Clinical response [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Defined as a > 50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease.

  • Combined rate of microscopic pathologic complete response and macroscopic pathologic complete response [ Time Frame: Monthly during neoadjuvant CHB and neoadjuvant chemotherapy (XMN) ] [ Designated as safety issue: No ]
    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: Every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.

  • Quantification of all grade 2, 3, 4 or fatal toxicity [ Time Frame: Weekly during CHB, neoadjuvant and adjuvant chemotherapy ] [ Designated as safety issue: Yes ]
  • Need for dose reduction treatment interruption or treatment discontinuation [ Time Frame: During adjuvant and neoadjuvant chemotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation of molecular markers with response, time to progression, and survival [ Time Frame: Weekly during CHB and XMN and pacitaxel ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: August 2005
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (hormone therapy and chemotherapy)
See detailed description
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00194792

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Hannah Linden Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00194792     History of Changes
Other Study ID Numbers: 6277, NCI-2010-00549
Study First Received: September 14, 2005
Last Updated: May 7, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Methotrexate
Capecitabine
Exemestane
Vinorelbine
Triptorelin Pamoate
Vinblastine
Paclitaxel
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 19, 2014