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

NCT00687648 | Unknown Phase 2

• 2 other identifiers: CDR0000595712SINGAPORE-NCC0706
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer; HER2-negative breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-positive breast cancer

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (5)

• 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

Study Arms (2)

Arm I

EXPERIMENTAL

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; Drug: cyclophosphamide; Drug: exemestane; Drug: letrozole; Drug: methotrexate; Drug: prednisolone

Arm II

ACTIVE COMPARATOR

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

Drug: cyclophosphamide; Drug: methotrexate; Drug: prednisolone

Interventions

anastrozole DRUG

Given as previously prescribed

Arm I

cyclophosphamide DRUG

Given by mouth

Arm I; Arm II

exemestane DRUG

Given as previously prescribed

Arm I

letrozole DRUG

Given as previously prescribed

Arm I

methotrexate DRUG

Given by mouth

Arm I; Arm II

prednisolone DRUG

Given by mouth

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre - Singapore

Singapore, 169610, Singapore

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; Cyclophosphamide; exemestane; Letrozole; Methotrexate; Prednisolone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Wong Nan Soon, MBBS, MRCP, FAMS

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 30, 2008
• First Posted: June 2, 2008
• Study Start: May 1, 2008
• Primary Completion: April 1, 2010
• Last Updated: June 17, 2009

Record last verified: 2009-06

Locations

SG (1)