Breast CancerPhase 2NCT00589238
Paclitaxel, Doxorubicin, and Cyclophosphamide With Or Without Carboplatin in Treating Women With Locally Advanced Breast Cancer That Can Be Removed by Surgery
A Phase 2 study testing carboplatin, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by National Cancer Centre, Singapore at 2 sites in Singapore.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, doxorubicin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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?
- carboplatin, cyclophosphamide and doxorubicin hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesSingapore
- Study dates
- Jan 2008to Jul 2012
- 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
- Menopausal status not specified
- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
- Life expectancy > 10 years
- Leukocytes ≥ 3,000/μL
- Absolute neutrophil count ≥ 1,500/μL
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- Platelets ≥ 100,000/μL
- Total bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Cardiac ejection fraction ≥ 50% as assessed by MUGA scan or 2D echocardiogram
Who cannot join
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, carboplatin, or other agents used in the study
- Pre-existing peripheral neuropathy
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
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- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
- Prior malignancies except for basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix
- PRIOR CONCURRENT THERAPY:
- No prior chemotherapy or radiotherapy
- No HIV-positive patients receiving combination antiretroviral therapy
- No concurrent primary growth factor prophylaxis
- No other concurrent investigational agents
- No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, surgery for cancer, or experimental medications
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites
National Cancer Centre - Singapore
Singapore, 169610
KK Women's and Children Hospital
Singapore
About this study
Official title: Randomised Phase II Trial of Neoadjuvant Weekly Paclitaxel Plus Carboplatin Compared to Weekly Paclitaxel Alone Followed in Both Arms by Doxorubicin and Cyclophosphamide for Operable or Locally Advanced Basal-like Subtype Breast Cancer Correlating BRCA-1 mRNA and Protein Expression With Carboplatin Response
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, doxorubicin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether combination chemotherapy is more effective with or without carboplatin in treating breast cancer.
PURPOSE: This randomized phase II trial is studying giving paclitaxel together with doxorubicin and cyclophosphamide to see how well it works compared to giving paclitaxel together with doxorubicin, cyclophosphamide, and carboplatin in treating women with locally advanced breast cancer that can be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate tumor pathological complete response rate after neoadjuvant paclitaxel with vs without carboplatin followed by cyclophosphamide and doxorubicin hydrochloride in women with basal-type subtype primary breast cancer.
Secondary
- To evaluate the clinical and pathological overall response rate.
- To evaluate safety and toxicity.
- To evaluate disease-free survival and overall survival.
- To correlate low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK 14, basal-like gene expression profile, and response to carboplatin-based treatment.
OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage (T2-3 vs T4). Patients are randomized to 1 of 2 treatment arms.
- Arm I (standard therapy): Patients receive paclitaxel IV over 1 hour once weekly in weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on days 1, 8, and 15. Treatment with doxorubicin hydrochloride and cyclophosphamide repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II (experimental therapy): Patients receive paclitaxel IV over 1 hour and carboplatin IV over 15 to 20 minutes on days 1, 8, and 15. Treatment with paclitaxel and carboplatin repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin hydrochloride and cyclophosphamide as in arm I.
All patients will then undergo surgical resection of the tumor.
Patients undergo biopsy for correlative studies. Samples are analyzed for estrogen receptor and progesterone receptor status, and molecular endpoints (CK 5/6, CK14, p53, BRCA, and EGFR) by RT-PCR, immunohistochemistry, protein expression, and gene expression profiling.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
- Conditions
- Breast Cancer
- Being tested
- carboplatin, cyclophosphamide, doxorubicin hydrochloride, paclitaxel
- Keywords
- stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC 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.
carboplatinDrug
cyclophosphamideDrug
paclitaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (Standard Arm) | Other | Arm 1 (Standard Arm) Preoperative (primary/ neoadjuvant) intravenous weekly paclitaxel 80 mg/m2 for 12 weeks followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles. Receives: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel |
| Arm 2 (Experimental Arm) | Experimental | Arm 2 (Experimental Arm) Preoperative intravenous weekly paclitaxel 80 mg/m2 in combination with carboplatin AUC 2 on D1, D8 and D15 every 28 days for 4 cycles followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles. Receives: Drug: carboplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response rate
Measured: Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.
Secondary outcomes (4)
Clinical and pathological overall response rates
Measured: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Overall and disease-free survival
Measured: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Incidence of each toxicity item
Measured: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Correlation between low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK14, basal like gene expression profile, and response to carboplatin based treatment
Measured: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2008 (estimated)
- Study startJan 2008
- Primary completionJul 2012
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
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yap Yoon Sim, National Cancer Centre, Singapore
- Investigators
- Wong Nan Soon, MBBS, MRCP, FAMS, Principal investigator, National Cancer Centre, SingaporeAnn Lee Siew Gek, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00589238
- Sponsor's protocol ID
- CDR0000579522
- Other IDs
- SINGAPORE-NCC-0701
- Status last verified
- Jun 2013
- First submitted
- 3 Jan 2008
- Last updated
- 19 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Phase II Trial of Neoadjuvant Weekly Paclitaxel Plus Carboplatin Compared to Weekly Paclitaxel Alone Followed in Both Arms by Doxorubicin and Cyclophosphamide for Operable or Locally Advanced Basal-like Subtype Breast Cancer Correlating BRCA-1 mRNA and Protein Expression With Carboplatin Response
- ClinicalTrials.gov ID
- NCT00589238
- Acronym / sponsor ID
- CDR0000579522
- Conditions
- Breast Cancer
- Keywords
- stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 16 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Jul 2012 (actual)
- First posted
- 9 Jan 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 paclitaxel, doxorubicin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether combination chemotherapy is more effective with or without carboplatin in treating breast cancer.
PURPOSE: This randomized phase II trial is studying giving paclitaxel together with doxorubicin and cyclophosphamide to see how well it works compared to giving paclitaxel together with doxorubicin, cyclophosphamide, and carboplatin in treating women with locally advanced breast cancer that can be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- To evaluate tumor pathological complete response rate after neoadjuvant paclitaxel with vs without carboplatin followed by cyclophosphamide and doxorubicin hydrochloride in women with basal-type subtype primary breast cancer.
Secondary
- To evaluate the clinical and pathological overall response rate.
- To evaluate safety and toxicity.
- To evaluate disease-free survival and overall survival.
- To correlate low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK 14, basal-like gene expression profile, and response to carboplatin-based treatment.
OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage (T2-3 vs T4). Patients are randomized to 1 of 2 treatment arms.
- Arm I (standard therapy): Patients receive paclitaxel IV over 1 hour once weekly in weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on days 1, 8, and 15. Treatment with doxorubicin hydrochloride and cyclophosphamide repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II (experimental therapy): Patients receive paclitaxel IV over 1 hour and carboplatin IV over 15 to 20 minutes on days 1, 8, and 15. Treatment with paclitaxel and carboplatin repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin hydrochloride and cyclophosphamide as in arm I.
All patients will then undergo surgical resection of the tumor.
Patients undergo biopsy for correlative studies. Samples are analyzed for estrogen receptor and progesterone receptor status, and molecular endpoints (CK 5/6, CK14, p53, BRCA, and EGFR) by RT-PCR, immunohistochemistry, protein expression, and gene expression profiling.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (Standard Arm) | Other | Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: paclitaxelArm 1 (Standard Arm) Preoperative (primary/ neoadjuvant) intravenous weekly paclitaxel 80 mg/m2 for 12 weeks followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles. |
| Arm 2 (Experimental Arm) | Experimental | Drug: carboplatin, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: paclitaxelArm 2 (Experimental Arm) Preoperative intravenous weekly paclitaxel 80 mg/m2 in combination with carboplatin AUC 2 on D1, D8 and D15 every 28 days for 4 cycles followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Female
- Menopausal status not specified
- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
- Life expectancy > 10 years
- Leukocytes ≥ 3,000/μL
Key exclusion criteria (15 listed)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, carboplatin, or other agents used in the study
- Pre-existing peripheral neuropathy
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Prior malignancies except for basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix
- No prior chemotherapy or radiotherapy
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 |
|---|---|---|
| carboplatin | Drug | Arm 2 (Experimental Arm) |
| cyclophosphamide | Drug | Arm 1 (Standard Arm), Arm 2 (Experimental Arm) |
| doxorubicin hydrochloride | Drug | Arm 1 (Standard Arm), Arm 2 (Experimental Arm) |
| paclitaxel | Drug | Arm 1 (Standard Arm), Arm 2 (Experimental Arm) |
Primary outcome
Pathological complete response rate
Time frame: Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.
4 secondary outcomes
Clinical and pathological overall response rates
Time frame: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Overall and disease-free survival
Time frame: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Incidence of each toxicity item
Time frame: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Correlation between low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK14, basal like gene expression profile, and response to carboplatin based treatment
Time frame: Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2013.
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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
Ann Lee Siew Gek principal investigator
National Cancer Centre, 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 carboplatin, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by National Cancer Centre, 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 13 inclusion and 15 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: stopped early, as of the sponsor's last update on 19 Jun 2013. 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?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response rate (time frame: Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.). 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 19 Jun 2013.