ErbB2-Positive Stage I-III Breast CancerPhase 2NCT01309607
Study of Preoperative Weekly Paclitaxel and Carboplatin With Lapatinib (Tykerb®) in Patients With ErbB2-Positive Stage I-III Breast Cancer
A Phase 2 study testing paclitaxel/carboplatin/lapatinib in people with ErbB2-Positive Stage I-III Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of weekly paclitaxel and carboplatin, in combination with lapatinib, in the neoadjuvant treatment of non-metastatic erbB2-positive breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- ErbB2-Positive Stage I-III Breast Cancer
- What is being tested?
- paclitaxel/carboplatin/lapatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteSingapore
- Study dates
- Apr 2011to Dec 2015
- 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
- T1-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with the largest diameter measuring 2.0cm or greater by calipers
- Tumor is HER2 positive either by IHC (3+) or FISH amplification (amplification ratio >2.2)
- Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer
- Karnofsky performance status of 70 or higher
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- Estimated life expectancy of at least 12 weeks
- 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
- Renal:
- o Calculated creatinine clearance >30ml/minute
- Left ventricular ejection fraction >=50% measured by 2D echo or MUGA
- Signed informed consent from patient or legal representative
- Patient 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
- Breast feeding
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- Serious cardiac illness or medical conditions including but not confined to:
- History of documented congestive cardiac failure or systolic dysfunction (LVEF <50%)
- High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV block, supraventricular arrhythmias which are not adequately rate-controlled)
- History of significant ischaemic heart disease
- Clinically significant valvular heart disease
- Poorly controlled hypertension (e.g. systolic BP > 180mmHg or diastolic >100mmHg)
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
- History of significant neurological or mental disorder, including seizures or dementia.
- Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment)
- Concomitant use of CYP3A4 inhibitors
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Open-Label Study of Preoperative Weekly Paclitaxel and Carboplatin With Lapatinib (Tykerb®) in Patients With ErbB2-Positive Stage I-III Breast Cancer
The purpose of this study is to evaluate the efficacy and safety of weekly paclitaxel and carboplatin, in combination with lapatinib, in the neoadjuvant treatment of non-metastatic erbB2-positive breast cancer.
Secondary objectives include:
Read more
- To determine the safety and tolerability of weekly paclitaxel and carboplatin, combined with lapatinib, in an Asian population
- To determine breast conservation rates following neoadjuvant paclitaxel/ carboplatin/ lapatinib
- To determine clinical response rates and relapse-free survival of patients treated with neoadjuvant paclitaxel/ carboplatin/ lapatinib
- To identify predictive tumour biomarkers for pathologic complete response
The investigators hypothesize that pathologic complete response rates will be improved from 15% to 35% with the neoadjuvant regimen of carboplatin/ paclitaxel/ lapatinib compared to standard chemotherapy alone in HER2 positive early stage breast cancers.
Read the detailed description
- Pathologic complete response following neoadjuvant chemotherapy has been shown to be an independent, strong predictor of disease-free and overall survival in operable breast cancer
- The addition of neoadjuvant trastuzumab to chemotherapy results in a 2-3 fold increase in pCR rates in operable ErbB2-positive breast cancer
- Lapatinib is being explored as an alternative to trastuzumab in large clinical trials in operable ErbB2-positive breast cancer
- In a randomised phase III adjuvant trial, BCIRG 006, non-anthracycline chemotherapy (docetaxel and carboplatin) has been shown to be as effective as conventional sequential anthracycline-containing chemotherapy and docetaxel, in combination with trastuzumab, but with improved cardiac safety
- Weekly paclitaxel has been shown in a randomized phase III study to be the optimal adjuvant taxane regimen
- Weekly paclitaxel and carboplatin, in combination with lapatinib, has demonstrated safety and efficacy in Phase I/II clinical studies of metastatic breast and ovarian cancer
- The investigators aim to assess the efficacy of a non-anthracycline containing regimen, weekly paclitaxel and carboplatin, in combination with lapatinib in inducing pCR in the neoadjuvant treatment of ErbB2-positive non-metastatic breast cancer. The investigators hypothesize that this combination will achieve pCR rates of at least 35%
- Conditions
- ErbB2-Positive Stage I-III Breast Cancer
- Being tested
- paclitaxel/carboplatin/lapatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
paclitaxel/carboplatin/lapatinibDrug
Drug doses for the neoadjuvant regimen:
- Paclitaxel 80mg/m2, day 1, 8, 15 of a 21-day cycle
- Carboplatin AUC of 2, day 1, 8 of a 21-day cycle
- Lapatinib 750mg daily continuously
| Study group | Role | What they receive |
|---|---|---|
| Pre-operative Therapy | Experimental | Neoadjuvant paclitaxel/carboplatin/lapatinib x 12 weeks Receives: Drug: paclitaxel/carboplatin/lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of pathologic complete response
Measured: 12 weeks
Secondary outcomes (5)
Treatment related toxicities
Measured: 12 weeks
Breast conservation rates
Measured: 16 weeks
Clinical response rates
Measured: 1 year
Relapse free survival (RFS)
Measured: 2 years
Identification of tumor biomarkers that predict pathologic complete response
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2011 (estimated)
- Study startApr 2011
- Primary completionDec 2014 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ErbB2-Positive Stage I-III Breast CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Centre, Singapore
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01309607
- Sponsor's protocol ID
- BR07/29/10
- Status last verified
- Oct 2014
- First submitted
- 3 Mar 2011
- Last updated
- 15 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. doi: 10.1200/JCO.1998.16.8.2672.
PubMed 9704717Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
PubMed 17192538
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Open-Label Study of Preoperative Weekly Paclitaxel and Carboplatin With Lapatinib (Tykerb®) in Patients With ErbB2-Positive Stage I-III Breast Cancer
- ClinicalTrials.gov ID
- NCT01309607
- Acronym / sponsor ID
- BR07/29/10
- Conditions
- ErbB2-Positive Stage I-III Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- National Cancer Centre, Singapore
- Study start
- Apr 2011
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 7 Mar 2011 (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.
The purpose of this study is to evaluate the efficacy and safety of weekly paclitaxel and carboplatin, in combination with lapatinib, in the neoadjuvant treatment of non-metastatic erbB2-positive breast cancer.
Secondary objectives include:
- To determine the safety and tolerability of weekly paclitaxel and carboplatin, combined with lapatinib, in an Asian population
- To determine breast conservation rates following neoadjuvant paclitaxel/ carboplatin/ lapatinib
- To determine clinical response rates and relapse-free survival of patients treated with neoadjuvant paclitaxel/ carboplatin/ lapatinib
- To identify predictive tumour biomarkers for pathologic complete response
The investigators hypothesize that pathologic complete response rates will be improved from 15% to 35% with the neoadjuvant regimen of carboplatin/ paclitaxel/ lapatinib compared to standard chemotherapy alone in HER2 positive early stage breast cancers.
Detailed description
- Pathologic complete response following neoadjuvant chemotherapy has been shown to be an independent, strong predictor of disease-free and overall survival in operable breast cancer
- The addition of neoadjuvant trastuzumab to chemotherapy results in a 2-3 fold increase in pCR rates in operable ErbB2-positive breast cancer
- Lapatinib is being explored as an alternative to trastuzumab in large clinical trials in operable ErbB2-positive breast cancer
- In a randomised phase III adjuvant trial, BCIRG 006, non-anthracycline chemotherapy (docetaxel and carboplatin) has been shown to be as effective as conventional sequential anthracycline-containing chemotherapy and docetaxel, in combination with trastuzumab, but with improved cardiac safety
- Weekly paclitaxel has been shown in a randomized phase III study to be the optimal adjuvant taxane regimen
- Weekly paclitaxel and carboplatin, in combination with lapatinib, has demonstrated safety and efficacy in Phase I/II clinical studies of metastatic breast and ovarian cancer
- The investigators aim to assess the efficacy of a non-anthracycline containing regimen, weekly paclitaxel and carboplatin, in combination with lapatinib in inducing pCR in the neoadjuvant treatment of ErbB2-positive non-metastatic breast cancer. The investigators hypothesize that this combination will achieve pCR rates of at least 35%
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pre-operative Therapy | Experimental | Drug: paclitaxel/carboplatin/lapatinibNeoadjuvant paclitaxel/carboplatin/lapatinib x 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- • Female, Age ≥ 18 years
- Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L
- Platelets >= 100 x 109/L
- Bilirubin <= 1.5 x upper limit of normal (ULN),
- ALT or AST <= 2.5x ULN
Key exclusion criteria (17 listed)
- • Prior treatment for locally advanced or metastatic breast cancer
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 |
|---|---|---|
| paclitaxel/carboplatin/lapatinibDrug doses for the neoadjuvant regimen: * Paclitaxel 80mg/m2, day 1, 8, 15 of a 21-day cycle * Carboplatin AUC of 2, day 1, 8 of a 21-day cycle * Lapatinib 750mg daily continuously | Drug | Pre-operative Therapy |
Primary outcome
Rate of pathologic complete response
Time frame: 12 weeks
5 secondary outcomes
Treatment related toxicities
Time frame: 12 weeks
Breast conservation rates
Time frame: 16 weeks
Clinical response rates
Time frame: 1 year
Relapse free survival (RFS)
Time frame: 2 years
Identification of tumor biomarkers that predict pathologic complete response
Time frame: 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2014.
- Background: PubMed 9704717Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. doi: 10.1200/JCO.1998.16.8.2672.
- Background: PubMed 17192538Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
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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 principal investigator
National University Hospital, 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 paclitaxel/carboplatin/lapatinib in people with ErbB2-Positive Stage I-III Breast Cancer, run by National University Hospital, 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?
The sponsor lists 19 inclusion and 17 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 15 Oct 2014. 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?
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?
Rate of pathologic complete response (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01309607, which also lists 2 linked publications.
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 15 Oct 2014.