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Cyclophosphamide, Methotrexate, and Prednisolone With or Without Aromatase Inhibitor Therapy in Treating Postmenopausal Women With Metastatic Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00687648
First received: May 30, 2008
Last updated: June 16, 2009
Last verified: June 2009
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, methotrexate, and prednisolone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole, letrozole, or exemestane may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether giving combination chemotherapy together with aromatase inhibitor therapy is more effective than combination chemotherapy alone in treating breast cancer.

PURPOSE: This randomized phase II trial is studying giving cyclophosphamide, methotrexate, and prednisolone together with aromatase inhibitor therapy to see how well it works compared with cyclophosphamide, methotrexate, and prednisolone in treating postmenopausal women with metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: anastrozole
Drug: cyclophosphamide
Drug: exemestane
Drug: letrozole
Drug: methotrexate
Drug: prednisolone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised Phase II Study of Metronomic Chemotherapy Plus the Same Aromatase Inhibitor Compared to Metronomic Chemotherapy Alone in Women With Hormone Receptor Positive, Her-2 Non-Overexpressing Advanced Breast Cancer Whose Disease Has Progressed While Receiving an Aromatase Inhibitor, Correlating Response With Circulating Endothelial Progenitor Cells, VEGF and VEGFR

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Clinical benefit response rate (complete response, partial response, or stable disease for > 24 weeks) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Safety and toxicity [ Designated as safety issue: Yes ]
  • Correlation between tumor response and markers of angiogenesis [ Designated as safety issue: No ]
  • Relative contribution of methotrexate and prednisolone to metronomic chemotherapy as assessed by change in circulating endothelial progenitor cell, VEGF, and VEGFR levels during serial addition of each drug [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: May 2008
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive aromatase inhibitor (anastrozole, letrozole, or exemestane) as previously prescribed. Patients also receive oral cyclophosphamide once daily on days 1-28 and oral methotrexate twice on days 15, 16, 22, and 23 of course 1. For all subsequent courses, patients receive oral cyclophosphamide once daily and oral prednisolone once daily on days 1-28 and oral methotrexate twice on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment with cyclophosphamide, methotrexate, and prednisolone repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: anastrozole
Given as previously prescribed
Drug: cyclophosphamide
Given by mouth
Drug: exemestane
Given as previously prescribed
Drug: letrozole
Given as previously prescribed
Drug: methotrexate
Given by mouth
Drug: prednisolone
Given by mouth
Active Comparator: Arm II
Patients receive cyclophosphamide, methotrexate, and prednisolone as in arm I.
Drug: cyclophosphamide
Given by mouth
Drug: methotrexate
Given by mouth
Drug: prednisolone
Given by mouth

Detailed Description:

OBJECTIVES:

Primary

  • Compare the clinical benefit rate (complete response, partial response or stable disease for > 24 weeks) in postmenopausal women with metastatic breast cancer treated with metronomic chemotherapy with vs without aromatase inhibitor therapy.

Secondary

  • Compare the time to progression in these patients
  • Compare the overall survival of these patients.
  • Compare the safety and toxicity of these regimens in these patients.
  • Correlate tumor response with markers of angiogenesis (circulating endothelial progenitor cells, VEGF, VEGF-C, VEGFR-2, and VEGFR-3).
  • Determine the relative contribution of methotrexate and prednisolone to metronomic chemotherapy as assessed by change in circulating endothelial progenitor cell, VEGF, and VEGFR levels during serial addition of each drug.

OUTLINE: Patients are stratified according to site of metastases (visceral vs non-visceral only) and number of lines of prior chemotherapy in the metastatic setting (0 vs 1-2). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive aromatase inhibitor (anastrozole, letrozole, or exemestane) as previously prescribed. Patients also receive oral cyclophosphamide once daily on days 1-28 and oral methotrexate twice on days 15, 16, 22, and 23 of course 1. For all subsequent courses, patients receive oral cyclophosphamide once daily and oral prednisolone once daily on days 1-28 and oral methotrexate twice on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment with cyclophosphamide, methotrexate, and prednisolone repeats every 28 days in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive cyclophosphamide, methotrexate, and prednisolone as in arm I.

Patients undergo blood sample collection at baseline, in weeks 2, 4, 6, and 10, every 4 weeks until disease progression, and then at 4 weeks after disease progression. Blood samples are assessed for circulating endothelial progenitor cell levels by flow cytometry and VEGF, VEGF-C, VEGFR-2, and VEGFR-3 levels by ELISA immunoassays.

After completion of study therapy, patients are followed every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer

    • Metastatic disease
  • Measurable disease, as defined by RECIST criteria
  • Evidence of disease progression while receiving a third-generation aromatase inhibitor
  • No extensive visceral disease (> 50% liver or lung parenchymal involvement)
  • No pleural effusion or ascites
  • No HER2/neu overexpression
  • Hormone receptor status:

    • Estrogen receptor- or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

  • Postmenopausal, as defined by any of the following:

    • Over 60 years of age
    • 50-59 years of age with plasma follicle-stimulating hormone, luteinizing hormone, and estradiol in the postmenopausal range and amenorrhea for > 1 year
    • Any age with documented bilateral oophorectomy
  • ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
  • Life expectancy > 6 months
  • Leukocytes ≥ 3,000/μL
  • Absolute neutrophil count ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Total bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant
  • Fertile patients must use effective contraception
  • No other prior malignancies except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, methotrexate, prednisolone, anastrozole, letrozole, or exemestane
  • No concurrent uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

  • No more than 2 lines of prior chemotherapy or endocrine therapy for advanced disease
  • No other concurrent chemotherapy, immunotherapy, anticancer hormonal therapy, or anticancer surgery
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
  • No concurrent combination anti-retroviral therapy for HIV-positive patients
  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: NCT00687648

Locations
Singapore
National Cancer Centre - Singapore Recruiting
Singapore, Singapore, 169610
Contact: Wong Nan Soon, MBBS, MRCP, FAMS    65-6-436-8088      
Sponsors and Collaborators
National Cancer Centre, Singapore
Investigators
Principal Investigator: Wong Nan Soon, MBBS, MRCP, FAMS National Cancer Centre, Singapore
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00687648     History of Changes
Other Study ID Numbers: CDR0000595712, SINGAPORE-NCC0706
Study First Received: May 30, 2008
Last Updated: June 16, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer
HER2-negative breast cancer
estrogen receptor-positive breast cancer
progesterone receptor-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Anastrozole
Aromatase Inhibitors
Cyclophosphamide
Exemestane
Letrozole
Methotrexate
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents

ClinicalTrials.gov processed this record on November 20, 2014