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

Primary Purpose

Breast Cancer

Status
Unknown status
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
anastrozole
cyclophosphamide
exemestane
letrozole
methotrexate
prednisolone
Sponsored by
National Cancer Centre, Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage IV breast cancer, recurrent breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer

Eligibility Criteria

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

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

Sites / Locations

  • National Cancer Centre - SingaporeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I

Arm II

Arm Description

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.

Patients receive cyclophosphamide, methotrexate, and prednisolone as in arm I.

Outcomes

Primary Outcome Measures

Clinical benefit response rate (complete response, partial response, or stable disease for > 24 weeks)

Secondary Outcome Measures

Time to progression
Overall survival
Safety and toxicity
Correlation between tumor response and markers of angiogenesis
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

Full Information

First Posted
May 30, 2008
Last Updated
June 16, 2009
Sponsor
National Cancer Centre, Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT00687648
Brief Title
Cyclophosphamide, Methotrexate, and Prednisolone With or Without Aromatase Inhibitor Therapy in Treating Postmenopausal Women With Metastatic Breast Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2009
Overall Recruitment Status
Unknown status
Study Start Date
May 2008 (undefined)
Primary Completion Date
April 2010 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Centre, Singapore

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
stage IV breast cancer, recurrent breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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 Title
Arm II
Arm Type
Active Comparator
Arm Description
Patients receive cyclophosphamide, methotrexate, and prednisolone as in arm I.
Intervention Type
Drug
Intervention Name(s)
anastrozole
Intervention Description
Given as previously prescribed
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
Given by mouth
Intervention Type
Drug
Intervention Name(s)
exemestane
Intervention Description
Given as previously prescribed
Intervention Type
Drug
Intervention Name(s)
letrozole
Intervention Description
Given as previously prescribed
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
Given by mouth
Intervention Type
Drug
Intervention Name(s)
prednisolone
Intervention Description
Given by mouth
Primary Outcome Measure Information:
Title
Clinical benefit response rate (complete response, partial response, or stable disease for > 24 weeks)
Secondary Outcome Measure Information:
Title
Time to progression
Title
Overall survival
Title
Safety and toxicity
Title
Correlation between tumor response and markers of angiogenesis
Title
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wong Nan Soon, MBBS, MRCP, FAMS
Organizational Affiliation
National Cancer Centre, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Centre - Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wong Nan Soon, MBBS, MRCP, FAMS
Phone
65-6-436-8088

12. IPD Sharing Statement

Learn more about this trial

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

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