Breast CancerPhase 2NCT00548184
Lapatinib and Trastuzumab With or Without Endocrine Therapy
A Phase 2 study testing Lapatinib, Trastuzumab and Endocrine in people with Breast Cancer, run by Baylor Breast Care Center at 6 sites in United States.
Trial summary
We think that lapatinib will help to shrink your tumor when given prior to the main or primary therapy for the kind of breast cancer you have been diagnosed with. When treatment is given before the main or primary therapy, it is called neoadjuvant therapy. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Lapatinib, Trastuzumab and Endocrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 6 sitesUnited States
- Study dates
- May 2008to Jan 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must be female.
- Signed informed consent.
- Locally advanced breast cancers or primary breast cancers are eligible. Locally advanced cancers must be of clinical and/or radiologic size >3 cm, or >2 cm with clinical evidence of axillary nodal involvement. (If tumors are less than 3 cm, we will use radiologically measured tumor size to determine the minimal tumor size for eligibility and in assessing tumor size during follow-up).
- HER2 overexpressing tumors defined as HercepTest score of 3+, or > 10% cells moderately or strongly HER2 positive by other methods, or Allred semi-quantitative score of >5, or gene amplified.
- Negative serum pregnancy test (HCG) within 7 days of starting study, if of child-bearing potential.
- Kidney and liver function tests - all within 1.5 times the institution's upper limit of normal.
Show all 11Show fewer
- Performance status (WHO scale) less than 2 and life expectancy more than 6 months.
- Age at least 18 years.
- No brain or leptomeningeal disease.
- No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
- Note: The presence of pathological involvement of axillary nodes will be assessed and agreed upon by two investigators.
Who cannot join
- Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
- Severe underlying chronic illness or disease.
- Cardiomyopathy or baseline LVEF less than 50%.
- Other investigational drugs while on study.
- Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded
- Taking any lapatinib-prohibited medication within 7 days of first dose of study medications. (See Prohibited Medications List in protocol.)
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bunting-Blaustein Cancer Research
Baltimore, Maryland, 21231-1000
UAB Cancer Center
Birmingham, Alabama, 35294
The University of Chicago
Chicago, Illinois, 60637
Baylor College of Medicine, Lester and Sue Smith Breast Center
Houston, Texas, 77030
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6868
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
About this study
Official title: A Phase II Trial of Lapatinib and Trastuzumab With or Without Endocrine Therapy in Locally Advanced HER2 Overexpressing Breast Cancer Patients
We think that lapatinib will help to shrink your tumor when given prior to the main or primary therapy for the kind of breast cancer you have been diagnosed with. When treatment is given before the main or primary therapy, it is called neoadjuvant therapy. We will compare lapatinib with lapatinib plus trastuzumab (herceptin) for 12 weeks. If your tumor is estrogen receptor positive (ER positive), estrogen deprivation will also be given to you. Tumors that are ER positive have a lot of estrogen receptors found in them. This is also called "over expression" or amplification of estrogen receptors.
The most important information we will get from this study is to see the response to "neoadjuvant" (treatment given before the main treatment), lapatinib with trastuzumab (herceptin) in your tumor tissue sample.
Read the detailed description
The neoadjuvant setting is especially attractive for studies of predictive biologic correlates for several reasons including early assessment of response to therapy, access to the primary tumor, and reduced patient numbers compared to those required in the adjuvant setting. Response to neoadjuvant therapy is a validated surrogate marker for improved survival; it may be used to test the overall efficacy of neoadjuvant treatment regimens and response in the primary tumor mirrors the effect of therapy on micrometastases.
Trastuzumab is an efficacious agent in HER2 overexpressing breast cancers. Our results with neoadjuvant trastuzumab indicate that its efficacy may be better in patients with treatment-naïve tumors compared to metastatic disease, with 26% of patients showing a partial response after only 3 weeks of therapy. No patients progressed during this 3-week period. We have also conducted a neoadjuvant lapatinib study given as a single agent for 6 weeks. The response rates in this second study have been impressive with greater than 80% responses in patients with HER2 positive locally advanced breast cancers. It is likely that the true response rate to HER2 blockade would be higher had therapy been continued for longer. We therefore hypothesize that lapatinib, a dual tyrosine kinase inhibitor, together with trastuzumab, will result in tumor regression when given as neoadjuvant therapy in HER2 overexpressing breast cancer. We will compare lapatinib plus trastuzumab for 12 weeks, and if the tumors express ER, estrogen deprivation will also be administered.
This is a phase II trial. Clinical efficacy will be assessed by bidimensional tumor measurements of the primary cancer at baseline, and at the end of week 12. Objective tumor response rate defined as objective bidimensional tumor measurements after neoadjuvant treatment at 12 weeks will be calculated, and assessed according to standard RECIST criteria. Pathologic responses will be graded as pathologic complete response if there is no invasive cancer in the residual breast at the time of surgery. Near pathologic complete response will also be documented as residual disease of less than 1 cm.
- Conditions
- Breast Cancer
- Being tested
- Lapatinib, Trastuzumab, Endocrine
- Keywords
- primary breast cancers, Locally advanced breast cancers
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LapatinibDrug
Also called TyKerb
Monoclonal Antibody
TrastuzumabDrug
Also called Herceptin
Monoclonal Antibody
EndocrineDrug
Also called Varies
Hormonal Therapy
| Study group | Role | What they receive |
|---|---|---|
| Single Group Assignment | Experimental | Lapatinib Trastuzumab Endocrine Receives: Drug: Lapatinib; Drug: Trastuzumab; Drug: Endocrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Assessment After Study Treatment
Pathologic Assessment After 12 weeks of lapatinib and trastuzumab with or without endocrine therapy. Pathologic complete response: no invasive cancer in the residual breast. Near pathologic complete response: residual disease of less than 1 cm in breast.
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 posted23 Oct 2007 (estimated)
- Study startMay 2008
- Primary completionJan 2011
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor Breast Care Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Mothaffar Rimawi, Baylor Breast Care Center
- Investigators
- Mothaffar Rimawi, MD, Principal investigator, Baylor Breast Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00548184
- Sponsor's protocol ID
- H-20464
- Status last verified
- Oct 2019
- First submitted
- 19 Oct 2007
- Last updated
- 7 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Veeraraghavan J, De Angelis C, Mao R, Wang T, Herrera S, Pavlick AC, Contreras A, Nuciforo P, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Wolff AC, Krop IE, Fuqua SAW, Prat A, Hilsenbeck SG, Weigelt B, Reis-Filho JS, Gutierrez C, Osborne CK, Rimawi MF, Schiff R. A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer. Ann Oncol. 2019 Jun 1;30(6):927-933. doi: 10.1093/annonc/mdz076.
PubMed 30903140Rimawi MF, Mayer IA, Forero A, Nanda R, Goetz MP, Rodriguez AA, Pavlick AC, Wang T, Hilsenbeck SG, Gutierrez C, Schiff R, Osborne CK, Chang JC. Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006. J Clin Oncol. 2013 May 10;31(14):1726-31. doi: 10.1200/JCO.2012.44.8027. Epub 2013 Apr 8.
PubMed 23569315
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Lapatinib and Trastuzumab With or Without Endocrine Therapy in Locally Advanced HER2 Overexpressing Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT00548184
- Acronym / sponsor ID
- H-20464
- Conditions
- Breast Cancer
- Keywords
- primary breast cancers, Locally advanced breast cancers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Baylor Breast Care CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- May 2008 (actual)
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 23 Oct 2007 (estimated)
- Results
- Posted 1 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We think that lapatinib will help to shrink your tumor when given prior to the main or primary therapy for the kind of breast cancer you have been diagnosed with. When treatment is given before the main or primary therapy, it is called neoadjuvant therapy. We will compare lapatinib with lapatinib plus trastuzumab (herceptin) for 12 weeks. If your tumor is estrogen receptor positive (ER positive), estrogen deprivation will also be given to you. Tumors that are ER positive have a lot of estrogen receptors found in them. This is also called "over expression" or amplification of estrogen receptors.
The most important information we will get from this study is to see the response to "neoadjuvant" (treatment given before the main treatment), lapatinib with trastuzumab (herceptin) in your tumor tissue sample.
Detailed description
The neoadjuvant setting is especially attractive for studies of predictive biologic correlates for several reasons including early assessment of response to therapy, access to the primary tumor, and reduced patient numbers compared to those required in the adjuvant setting. Response to neoadjuvant therapy is a validated surrogate marker for improved survival; it may be used to test the overall efficacy of neoadjuvant treatment regimens and response in the primary tumor mirrors the effect of therapy on micrometastases.
Trastuzumab is an efficacious agent in HER2 overexpressing breast cancers. Our results with neoadjuvant trastuzumab indicate that its efficacy may be better in patients with treatment-naïve tumors compared to metastatic disease, with 26% of patients showing a partial response after only 3 weeks of therapy. No patients progressed during this 3-week period. We have also conducted a neoadjuvant lapatinib study given as a single agent for 6 weeks. The response rates in this second study have been impressive with greater than 80% responses in patients with HER2 positive locally advanced breast cancers. It is likely that the true response rate to HER2 blockade would be higher had therapy been continued for longer. We therefore hypothesize that lapatinib, a dual tyrosine kinase inhibitor, together with trastuzumab, will result in tumor regression when given as neoadjuvant therapy in HER2 overexpressing breast cancer. We will compare lapatinib plus trastuzumab for 12 weeks, and if the tumors express ER, estrogen deprivation will also be administered.
This is a phase II trial. Clinical efficacy will be assessed by bidimensional tumor measurements of the primary cancer at baseline, and at the end of week 12. Objective tumor response rate defined as objective bidimensional tumor measurements after neoadjuvant treatment at 12 weeks will be calculated, and assessed according to standard RECIST criteria. Pathologic responses will be graded as pathologic complete response if there is no invasive cancer in the residual breast at the time of surgery. Near pathologic complete response will also be documented as residual disease of less than 1 cm.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Group Assignment | Experimental | Drug: Lapatinib, Drug: Trastuzumab, Drug: EndocrineLapatinib Trastuzumab Endocrine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- All patients must be female.
- Signed informed consent.
- Locally advanced breast cancers or primary breast cancers are eligible. Locally advanced cancers must be of clinical and/or radiologic size >3 cm, or >2 cm with clinical evidence of axillary nodal involvement. (If tumors are less than 3 cm, we will use radiologically measured tumor size to determine the minimal tumor size for eligibility and in assessing tumor size during follow-up).
- HER2 overexpressing tumors defined as HercepTest score of 3+, or > 10% cells moderately or strongly HER2 positive by other methods, or Allred semi-quantitative score of >5, or gene amplified.
- Negative serum pregnancy test (HCG) within 7 days of starting study, if of child-bearing potential.
Key exclusion criteria (7 listed)
- Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
- Severe underlying chronic illness or disease.
- Cardiomyopathy or baseline LVEF less than 50%.
- Other investigational drugs while on study.
- Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease.
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 |
|---|---|---|
| LapatinibAlso: TyKerbMonoclonal Antibody | Drug | Single Group Assignment |
| TrastuzumabAlso: HerceptinMonoclonal Antibody | Drug | Single Group Assignment |
| EndocrineAlso: VariesHormonal Therapy | Drug | Single Group Assignment |
Primary outcome
Pathologic Assessment After Study Treatment
Time frame: 12 weeks
Pathologic Assessment After 12 weeks of lapatinib and trastuzumab with or without endocrine therapy. Pathologic complete response: no invasive cancer in the residual breast. Near pathologic complete response: residual disease of less than 1 cm in breast.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30903140Veeraraghavan J, De Angelis C, Mao R, Wang T, Herrera S, Pavlick AC, Contreras A, Nuciforo P, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Wolff AC, Krop IE, Fuqua SAW, Prat A, Hilsenbeck SG, Weigelt B, Reis-Filho JS, Gutierrez C, Osborne CK, Rimawi MF, Schiff R. A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer. Ann Oncol. 2019 Jun 1;30(6):927-933. doi: 10.1093/annonc/mdz076.
- Derived from this study: PubMed 23569315Rimawi MF, Mayer IA, Forero A, Nanda R, Goetz MP, Rodriguez AA, Pavlick AC, Wang T, Hilsenbeck SG, Gutierrez C, Schiff R, Osborne CK, Chang JC. Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006. J Clin Oncol. 2013 May 10;31(14):1726-31. doi: 10.1200/JCO.2012.44.8027. Epub 2013 Apr 8.
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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.
Mothaffar Rimawi, MD principal investigator
Baylor Breast Center
6 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 Lapatinib, Trastuzumab and Endocrine in people with Breast Cancer, run by Baylor Breast Care Center at 6 sites in United States.
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 11 inclusion and 7 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: finished, as of the sponsor's last update on 7 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. 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?
Yes. Results are posted in the registry (first posted 1 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Pathologic Assessment After Study Treatment (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 NCT00548184, 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 7 Nov 2019.