Breast CancerPhase 2NCT00687648
Cyclophosphamide, Methotrexate, and Prednisolone With or Without Aromatase Inhibitor Therapy in Treating Postmenopausal Women With Metastatic Breast Cancer
A Phase 2 study testing anastrozole, cyclophosphamide and exemestane in people with Breast Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- anastrozole, cyclophosphamide and exemestane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteSingapore
- Study dates
- May 2008to Apr 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National Cancer Centre - Singapore
Singapore, 169610
Wong Nan Soon, MBBS, MRCP, FAMS, 65-6-436-8088
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- anastrozole, cyclophosphamide, exemestane, letrozole, methotrexate
- Keywords
- stage IV breast cancer, recurrent breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anastrozoleDrug
Given as previously prescribed
cyclophosphamideDrug
Given by mouth
exemestaneDrug
Given as previously prescribed
letrozoleDrug
Given as previously prescribed
methotrexateDrug
Given by mouth
prednisoloneDrug
Given by mouth
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: cyclophosphamide; Drug: methotrexate; Drug: prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionApr 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Investigators
- Wong Nan Soon, MBBS, MRCP, FAMS, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00687648
- Sponsor's protocol ID
- CDR0000595712
- Other IDs
- SINGAPORE-NCC0706
- Status last verified
- Jun 2009
- First submitted
- 30 May 2008
- Last updated
- 17 Jun 2009
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00687648
- Acronym / sponsor ID
- CDR0000595712
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Apr 2010 (estimated)
- First posted
- 2 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: anastrozole, Drug: cyclophosphamide, Drug: exemestane, Drug: letrozole, Drug: methotrexate, Drug: prednisolonePatients 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 | Active comparator | Drug: cyclophosphamide, Drug: methotrexate, Drug: prednisolonePatients receive cyclophosphamide, methotrexate, and prednisolone as in arm I. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anastrozoleGiven as previously prescribed | Drug | Arm I |
| cyclophosphamideGiven by mouth | Drug | Arm I, Arm II |
| exemestaneGiven as previously prescribed | Drug | Arm I |
| letrozoleGiven as previously prescribed | Drug | Arm I |
| methotrexateGiven by mouth | Drug | Arm I, Arm II |
| prednisoloneGiven by mouth | Drug | Arm I, Arm II |
Primary outcome
Clinical benefit response rate (complete response, partial response, or stable disease for > 24 weeks)
5 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wong Nan Soon, MBBS, MRCP, FAMS principal investigator
National Cancer Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing anastrozole, cyclophosphamide and exemestane in people with Breast Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jun 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical benefit response rate (complete response, partial response, or stable disease for > 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2009.