Breast CancerPhase 2NCT01176799
Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor
A Phase 2 study testing Arm A and Arm B in people with Breast Cancer, run by National University Hospital, Singapore at 2 sites in Singapore.
Trial summary
This is a single-centre, phase II randomized study of doxorubicin and cyclophosphamide (AC) with or without intermittent sunitinib in patients with measurable primary breast cancer who are receiving pre-operative chemotherapy. 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?
- Arm A and Arm B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 2 sitesSingapore
- Study dates
- Aug 2010to Dec 2017
- 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
Who may be able to join
- Female, age >= 18 years.
- Histologic or cytologic diagnosis of breast carcinoma.
- T2-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
- Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
- Karnofsky performance status of 70 or higher.
- Estimated life expectancy of at least 12 weeks.
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- Adequate organ function including the following:
- Bone marrow:
- Absolute neutrophil (segmented and bands) count (ANC) >=1.5 x 109/L
- Platelets >= 100 x 109/L
- Hepatic:
- Bilirubin <= 1.5 x upper limit of normal (ULN),
- ALT or AST <= 2.5x ULN, (or <= 5 X with liver metastases)
- Renal:
- Creatinine <= 1.5x ULN
- Left ventricular ejection fraction >=50%
- Signed informed consent from patient or legal representative.
- Patients with reproductive potential must use an approved contraceptive method if appropriate (e.g., intrauterine device, birth control pills, or barrier device) during and for three months after the study.Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
Who cannot join
- Prior treatment for locally advanced or metastatic breast cancer.
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Major surgery within 28 days of study drug administration.
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Pregnancy.
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- Breast feeding.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- Active bleeding disorder or bleeding site.
- Non-healing wound.
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
- Known history of systemic connective tissue diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis), vasculitides (e.g., giant cell arteritis, Kawasaki disease, Wegener's granulomatosis, Churg-Strauss disease) or sickle cell disease.
- Known history of renal impairment, defined as a Glomerular Filtration Rate (GFR) of less than 30ml/minute.
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites, 2 recruiting
- Recruiting
National University Hospital
Singapore, Singapore, 119074
Soo Chin Lee, MBBS, MRCP, 65 6772 4629, Soo_Chin_Lee@nuhs.edu.sg
Soo Chin Lee, MBBS, MRCP
- Recruiting
National University Hospital
Singapore, Singapore, 119228
About this study
Official title: Phase II Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor
This is a single-centre, phase II randomized study of doxorubicin and cyclophosphamide (AC) with or without intermittent sunitinib in patients with measurable primary breast cancer who are receiving pre-operative chemotherapy.
A lead-in phase I study was built into this protocol to determine the dose and duration of sunitinib that may achieve the desired effects of normalizing tumor vasculature prior to chemotherapy administration.
Read more
A total of 64 patients with measurable primary tumor will be enrolled for the Phase II part of the study. Eligible patients will be randomized 1:1 to either arm A or arm B. Patients will be stratified according to metastatic status (metastatic vs non-metastatic) and presence or absence of clinical T4 disease.
Arm A (Control arm):
Doxorubicin 60mg/m2 day 1 Cyclophosphamide 600mg/m2 day1, every 3 weeks x 4 cycles
Arm B (Experimental arm):
Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily (duration and dose as determined from the lead-in phase I study) Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2)
DCE-MRI scan will be performed serially to determine tumor response and change in tumor vascular parameters for each enrolled subject:
Patient will be evaluated weekly for toxicity assessments and full blood count during cycle 1, and on days 1 and 15 of each subsequent cycle. In addition, patients in Arm B will be evaluated weekly during the first two weeks of sunitinib administration prior to cycle 1 AC.
Read the detailed description
Special tests Blood sampling
- Germline DNA at baseline for pharmacogenetics analysis.
- Pharmacokinetic sampling for doxorubicin and cyclophosphamide on day 1, cycle 1 of AC administration.
- Pharmacokinetic sampling for sunitinib at baseline and weekly during the first course of sunitinib for subjects in Arm B before the sunitinib dose on that day.
- Serial plasma samples for proteomics analysis and for analysis of soluble angiogenic factors
- Serial whole blood for gene expression analysis
- Serial blood samples for circulating tumor and circulating endothelial cells
- DNA will be extracted from collected snap-frozen and/or paraffin-embedded tumor tissue sections (pre- and post-treatment) and plasma (pre- and post-treatment taken for plasma biomarker analysis). Primary tumor and circulating tumor DNA will be genotyped for cancer genes of interest that may influence cancer prognosis and/or treatment response.
Tumor core biopsy Arm A: Performed at baseline, approximately 3 weekly after cycle 1 AC but before cycle 2 AC, and upon completion of 4 cycles of AC, for a total of 3 tumor core biopsies Arm B: Performed at baseline, after completing the first course of sunitinib and before cycle 1 AC, approximately 3 weekly after cycle 1 AC but before cycle 2 AC, and upon completion of 4 cycles of AC, for a total of 4 tumor core biopsies.
The final biopsy may be obtained at surgery if the patient is scheduled for lumpectomy or mastectomy. The tumor cores will be stored in liquid nitrogen for subsequent DNA, RNA and protein extraction for biomarker studies including gene expression and proteomics analyses. Three to four samples will be obtained at each time point, and one tumor core at each time point will be stored in formalin and paraffin-embedded for immunohistochemistry analysis of biomarkers.
Note: Tumor biopsies, imaging and blood collection that are to be conducted after completing the first course of sunitinib may be carried out as early as 2 days before the last dose of sunitinib in the first course for logistics reasons.
- Conditions
- Breast Cancer
- Being tested
- Arm A, Arm B
- Keywords
- Breast cancer patients with measurable primary breast cancer tumor.
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm ADrug
Also called Control Arm, Doxorubicin and Cyclophosphamide
Doxorubicin 60mg/m2 day 1 Cyclophosphamide 600mg/m2 day1, every 3 weeks x 4 cycles
Arm BDrug
Also called Experimental Arm:, Sunitinib and doxorubicin and cyclophosphamide (AC)
Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2)
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Control Arm | Active comparator | Doxorubicin - 60mg/m2 day 1
Cyclophosphamide
-600mg/m2 day1, every 3 weeks x 4 cycles Receives: Drug: Arm A |
| Arm B: Experimental | Experimental | Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2) Receives: Drug: Arm B |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological complete response rate
To compare the pathological complete response rate of doxorubicin/cyclophosphamide with or without intermittent sunitinib in the first-line pre-operative setting in breast cancer in the Phase II part of the study.
Measured: 12 weeks
Secondary outcomes (1)
clinical response rate
To compare the clinical response rate (complete and partial response) and progression-free survival in patients treated with 4 cycles of doxorubicin/cyclophosphamide with or without intermittent sunitinib in the first-line pre-operative setting in breast cancer
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionDec 2016 (estimated)
- Study completionDec 2017 (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
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 73 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, MBBS, MRCP, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01176799
- Sponsor's protocol ID
- BR01/09/10
- Status last verified
- Jun 2016
- First submitted
- 5 Aug 2010
- Last updated
- 22 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor
- ClinicalTrials.gov ID
- NCT01176799
- Acronym / sponsor ID
- BR01/09/10
- Conditions
- Breast Cancer
- Keywords
- Breast cancer patients with measurable primary breast cancer tumor.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 73 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 6 Aug 2010 (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.
This is a single-centre, phase II randomized study of doxorubicin and cyclophosphamide (AC) with or without intermittent sunitinib in patients with measurable primary breast cancer who are receiving pre-operative chemotherapy.
A lead-in phase I study was built into this protocol to determine the dose and duration of sunitinib that may achieve the desired effects of normalizing tumor vasculature prior to chemotherapy administration.
A total of 64 patients with measurable primary tumor will be enrolled for the Phase II part of the study. Eligible patients will be randomized 1:1 to either arm A or arm B. Patients will be stratified according to metastatic status (metastatic vs non-metastatic) and presence or absence of clinical T4 disease.
Arm A (Control arm):
Doxorubicin 60mg/m2 day 1 Cyclophosphamide 600mg/m2 day1, every 3 weeks x 4 cycles
Arm B (Experimental arm):
Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily (duration and dose as determined from the lead-in phase I study) Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2)
DCE-MRI scan will be performed serially to determine tumor response and change in tumor vascular parameters for each enrolled subject:
Patient will be evaluated weekly for toxicity assessments and full blood count during cycle 1, and on days 1 and 15 of each subsequent cycle. In addition, patients in Arm B will be evaluated weekly during the first two weeks of sunitinib administration prior to cycle 1 AC.
Detailed description
Special tests Blood sampling
- Germline DNA at baseline for pharmacogenetics analysis.
- Pharmacokinetic sampling for doxorubicin and cyclophosphamide on day 1, cycle 1 of AC administration.
- Pharmacokinetic sampling for sunitinib at baseline and weekly during the first course of sunitinib for subjects in Arm B before the sunitinib dose on that day.
- Serial plasma samples for proteomics analysis and for analysis of soluble angiogenic factors
- Serial whole blood for gene expression analysis
- Serial blood samples for circulating tumor and circulating endothelial cells
- DNA will be extracted from collected snap-frozen and/or paraffin-embedded tumor tissue sections (pre- and post-treatment) and plasma (pre- and post-treatment taken for plasma biomarker analysis). Primary tumor and circulating tumor DNA will be genotyped for cancer genes of interest that may influence cancer prognosis and/or treatment response.
Tumor core biopsy Arm A: Performed at baseline, approximately 3 weekly after cycle 1 AC but before cycle 2 AC, and upon completion of 4 cycles of AC, for a total of 3 tumor core biopsies Arm B: Performed at baseline, after completing the first course of sunitinib and before cycle 1 AC, approximately 3 weekly after cycle 1 AC but before cycle 2 AC, and upon completion of 4 cycles of AC, for a total of 4 tumor core biopsies.
The final biopsy may be obtained at surgery if the patient is scheduled for lumpectomy or mastectomy. The tumor cores will be stored in liquid nitrogen for subsequent DNA, RNA and protein extraction for biomarker studies including gene expression and proteomics analyses. Three to four samples will be obtained at each time point, and one tumor core at each time point will be stored in formalin and paraffin-embedded for immunohistochemistry analysis of biomarkers.
Note: Tumor biopsies, imaging and blood collection that are to be conducted after completing the first course of sunitinib may be carried out as early as 2 days before the last dose of sunitinib in the first course for logistics reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Control Arm | Active comparator | Drug: Arm ADoxorubicin - 60mg/m2 day 1 Cyclophosphamide -600mg/m2 day1, every 3 weeks x 4 cycles |
| Arm B: Experimental | Experimental | Drug: Arm BDays -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Female, age >= 18 years.
- Histologic or cytologic diagnosis of breast carcinoma.
- T2-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
- Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
- Karnofsky performance status of 70 or higher.
Key exclusion criteria (16 listed)
- Prior treatment for locally advanced or metastatic breast cancer.
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Major surgery within 28 days of study drug administration.
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
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 |
|---|---|---|
| Arm AAlso: Control Arm, Doxorubicin and CyclophosphamideDoxorubicin 60mg/m2 day 1 Cyclophosphamide 600mg/m2 day1, every 3 weeks x 4 cycles | Drug | Arm A: Control Arm |
| Arm BAlso: Experimental Arm:, Sunitinib and doxorubicin and cyclophosphamide (AC)Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2) | Drug | Arm B: Experimental |
Primary outcome
pathological complete response rate
Time frame: 12 weeks
To compare the pathological complete response rate of doxorubicin/cyclophosphamide with or without intermittent sunitinib in the first-line pre-operative setting in breast cancer in the Phase II part of the study.
1 secondary outcome
clinical response rate
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2016.
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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.
Soo Chin Lee, MBBS, MRCP principal investigator
National University Hospital, Singapore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arm A and Arm B in people with Breast Cancer, run by National University Hospital, Singapore at 2 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. 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 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Contact Soo Chin Lee, MBBS, MRCP (65 6772 4629, Soo_Chin_Lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological complete response rate (time frame: 12 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 22 Jun 2016; AzTrials last refreshed its copy on 26 Oct 2026.