Breast CancerPhase 2NCT00470704
Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer
A Phase 2 study testing Lapatinib and Herceptin in people with Breast Cancer, run by Nancy Lin, MD at 9 sites in United States.
Trial summary
In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Lapatinib and Herceptin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 9 sitesUnited States
- Study dates
- 14 May 2007to 20 Aug 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed invasive breast cancer, with stage IV disease
- HER2-positive breast cancer, defined as 3+ staining by IHC or gene amplification by FISH
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
- Willingness to undergo a research biopsy of recurrent or metastatic disease
- Prior chemotherapy treatment must be discontinued for at least 2 weeks prior to study entry.
- Completed radiation therapy at least 7 days prior to beginning protocol treatment
Show all 14Show fewer
- Cohort 1: No prior chemotherapy for advanced breast cancer; no prior trastuzumab in the advanced breast cancer setting; nor prior treatment with lapatinib or other HER2-directed therapy other than trastuzumab
- Cohort 2: Up to two prior chemotherapy regimens for the treatment of advanced breast cancer; no prior treatment with lapatinib or other HER2-directed therapy except for trastuzumab
- 18 years of age or older
- Life expectancy of greater than 12 weeks
- ECOG Performance Status 0-2
- Normal organ and marrow function as outlined in protocol
- Cardiac ejection fraction, as assessed by either MUGA scan or echocardiogram greater than or equal to 50%
- Able to take oral medications
Who cannot join
- Patients may not be receiving any other investigational agents or concurrent chemotherapy or hormonal therapy for treatment of metastatic disease
- Active brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in this study
- Clinically significant malabsorption syndrome
- Uncontrolled intercurrent illness
- Pregnant or breastfeeding women
- Concurrent use of the medications listed in the protocol because of possible interaction with lapatinib
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University fo Alabama at Birmingham
Birmingham, Alabama, 35294
Dana-Farber at Faulkner Hospital
Boston, Massachusetts, 02130
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Chicago
Chicago, Illinois, 60452
Baylor College of Medicine
Houston, Texas, 77030
Vanderbilt University
Nashville, Tennessee, 37232
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: A Phase 2 Study of Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer
In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Finally, we are studying genes and proteins in the tumor tissue that may lead to sensitivity or resistance to Herceptin, and to the combination of Herceptin plus lapatinib. Lapatinib is a compound that may stop cancer cells from growing. Other research studies suggest that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer.
Read the detailed description
- Participants will be asked to undergo a biopsy of an area of the body where the cancer has spread.
- Participants will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks during which time you will be taking lapatinib, once per day.
- Participants will receive Herceptin once every week or once every 3 weeks through a vein.
- During all treatment cycles a physical exam will be performed and questions about the participants general health will be asked. Blood tests including chemistry and hematology will be performed to measure additional effect of the study drug and disease status. Photographs may be taken of the tumor to assess the response of the tumor to treatment.
- CT scans will be repeated every 8 weeks to assess the effect of the study treatment on the cancer. Either a MUGA scan or echocardiogram will be performed 8 weeks and 16 weeks after the participant starts the study treatment.
- Participants will remain on this research study for as long as they are benefiting from the study treatment.
- Conditions
- Breast Cancer
- Being tested
- Lapatinib, Herceptin
- Keywords
- HER2-positive breast cancer, Herceptin, trastuzumab
- 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
HerceptinDrug
Also called trastuzumab
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Other | This cohort is made up of participants without prior trastuzumab for MBC. Adjuvant or neoadjuvant trastuzumab was allowed, if the interval from trastuzumab completion to recurrence exceeded 1 year.
1000 mg daily Lapatinib
2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab Receives: Drug: Lapatinib; Drug: Herceptin |
| Cohort 2 | Other | This cohort is made up of participants with one to two lines of chemotherapy for metastatic disease with at least one trastuzumab-containing regimen or patients who recurred within 12 months of adjuvant or neoadjuvant trastuzumab with up to one line of metastatic trastuzumab-based therapy
1000 mg daily Lapatinib
2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab Receives: Drug: Lapatinib; Drug: Herceptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
The objective response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria.
CR and PR must meet the following lesion criteria without having any new lesions as well:
Target Lesion:
(CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
(PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Non-Target Lesion:
(CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.
Measured: 8 weeks
Secondary outcomes (5)
Top 3 Most Common Treatment RelatedToxicities
Assessed by -Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Top 3 treatment-related all-grade adverse events in terms of incidence.
Treatment Related is discerned as follows:
Yes: There is a plausible temporal relationship between the onset of the AE and administration of atezolizumab or bevacizumab, and the AE cannot be readily explained by the patient's clinical state, intercurrent illness, or concomitant therapies; and/or the AE follows a known pattern of response to atezolizumab or bevacizumab or with similar treatments; and/or the AE resolves upon discontinuation of the study drugs or dose reduction and, if applicable, reappears upon re-challenge.
No: Evidence exists that the AE has an etiology other than the study drugs (e.g., pre existing medical condition, underlying disease, intercurrent illness, or concomitant medication); and/or the AE has no plausible temporal relationship to the study drugs administration.
Measured: Up to 93 months
Sites of First Progression
Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST) as follows:
- >20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including baseline if it's the smallest). The sum must also demonstrate an increase of >5 mm.
OR
-Appearance of new lesions and/or unequivocal progression of non-target lesions. It must be representative of overall disease status change, not a single lesion increase. For patients with PD at the first on-treatment imaging assessment, patients will be allowed to remain on study until confirmation at the next assessment at investigator discretion if patient is benefiting from treatment.
Measured: Up to 93 months
Clinical Benefit Rate
Clinical Benefit Rate is the percentage of participants who achieve clinical benefit from the study treatment. Clinical benefit is defined as at least 24 weeks of confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD).
SD or better is achieved if the following are true:
Target Lesions:
-At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Non-target Lesions:
No progression. No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Measured: Up to 93 months
3-Year Overall Survival
Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. 3-Year survival is calculated using Kaplan-Meier methods.
Measured: Up to 93 months
Median Time to Progression
Time to progression (TTP) is defined as the time from study entry to disease progression by RECIST. Subjects are considered to have progressed if they discontinue treatment due to clinical deterioration from breast cancer or die on-treatment of any cause. TTP is censored at the time of initiation of alternative therapy or time of last contact. The time to progression is calculated using a Kaplan-Meier emthods.
Progression is defined by RECIST as:
>20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including baseline if it's the smallest). The sum must also demonstrate an increase of >5 mm.
OR Appearance of new lesions and/or unequivocal progression of non-target lesions. It must be representative of overall disease status change, not a single lesion increase.
Measured: Up to 93 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2007 (estimated)
- Study start14 May 2007
- Primary completion30 Nov 2013
- Study completion20 Aug 2024
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 (1)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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nancy Lin, MD
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Novartis
- Responsible party
- Sponsor-investigator, Nancy Lin, MD, Dana-Farber Cancer Institute
- Investigators
- Nancy Lin, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00470704
- Sponsor's protocol ID
- 06-213
- Status last verified
- Dec 2024
- First submitted
- 7 May 2007
- Last updated
- 19 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Lin NU, Guo H, Yap JT, Mayer IA, Falkson CI, Hobday TJ, Dees EC, Richardson AL, Nanda R, Rimawi MF, Ryabin N, Najita JS, Barry WT, Arteaga CL, Wolff AC, Krop IE, Winer EP, Van den Abbeele AD. Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003). J Clin Oncol. 2015 Aug 20;33(24):2623-31. doi: 10.1200/JCO.2014.60.0353. Epub 2015 Jul 13.
PubMed 26169615
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00470704
- Acronym / sponsor ID
- 06-213
- Conditions
- Breast Cancer
- Keywords
- HER2-positive breast cancer, Herceptin, trastuzumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Nancy Lin, MDUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Novartis
- Study start
- 14 May 2007 (actual)
- Primary completion
- 30 Nov 2013 (actual)
- Study completion
- 20 Aug 2024 (actual)
- First posted
- 8 May 2007 (estimated)
- Results
- Posted 15 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Finally, we are studying genes and proteins in the tumor tissue that may lead to sensitivity or resistance to Herceptin, and to the combination of Herceptin plus lapatinib. Lapatinib is a compound that may stop cancer cells from growing. Other research studies suggest that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer.
Detailed description
- Participants will be asked to undergo a biopsy of an area of the body where the cancer has spread.
- Participants will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks during which time you will be taking lapatinib, once per day.
- Participants will receive Herceptin once every week or once every 3 weeks through a vein.
- During all treatment cycles a physical exam will be performed and questions about the participants general health will be asked. Blood tests including chemistry and hematology will be performed to measure additional effect of the study drug and disease status. Photographs may be taken of the tumor to assess the response of the tumor to treatment.
- CT scans will be repeated every 8 weeks to assess the effect of the study treatment on the cancer. Either a MUGA scan or echocardiogram will be performed 8 weeks and 16 weeks after the participant starts the study treatment.
- Participants will remain on this research study for as long as they are benefiting from the study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Other | Drug: Lapatinib, Drug: HerceptinThis cohort is made up of participants without prior trastuzumab for MBC. Adjuvant or neoadjuvant trastuzumab was allowed, if the interval from trastuzumab completion to recurrence exceeded 1 year. 1000 mg daily Lapatinib 2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab |
| Cohort 2 | Other | Drug: Lapatinib, Drug: HerceptinThis cohort is made up of participants with one to two lines of chemotherapy for metastatic disease with at least one trastuzumab-containing regimen or patients who recurred within 12 months of adjuvant or neoadjuvant trastuzumab with up to one line of metastatic trastuzumab-based therapy 1000 mg daily Lapatinib 2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically or cytologically confirmed invasive breast cancer, with stage IV disease
- HER2-positive breast cancer, defined as 3+ staining by IHC or gene amplification by FISH
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
- Willingness to undergo a research biopsy of recurrent or metastatic disease
- Prior chemotherapy treatment must be discontinued for at least 2 weeks prior to study entry.
Key exclusion criteria (7 listed)
- Patients may not be receiving any other investigational agents or concurrent chemotherapy or hormonal therapy for treatment of metastatic disease
- Active brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in this study
- Clinically significant malabsorption syndrome
- Uncontrolled intercurrent illness
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: Tykerb | Drug | Cohort 1, Cohort 2 |
| HerceptinAlso: trastuzumab | Drug | Cohort 1, Cohort 2 |
Primary outcome
Objective Response Rate
Time frame: 8 weeks
The objective response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.
5 secondary outcomes
Top 3 Most Common Treatment RelatedToxicities
Time frame: Up to 93 months
Sites of First Progression
Time frame: Up to 93 months
Clinical Benefit Rate
Time frame: Up to 93 months
3-Year Overall Survival
Time frame: Up to 93 months
Median Time to Progression
Time frame: Up to 93 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26169615Lin NU, Guo H, Yap JT, Mayer IA, Falkson CI, Hobday TJ, Dees EC, Richardson AL, Nanda R, Rimawi MF, Ryabin N, Najita JS, Barry WT, Arteaga CL, Wolff AC, Krop IE, Winer EP, Van den Abbeele AD. Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003). J Clin Oncol. 2015 Aug 20;33(24):2623-31. doi: 10.1200/JCO.2014.60.0353. Epub 2015 Jul 13.
- Individual participant dataSharing planned: Undecided
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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.
Nancy Lin, MD principal investigator
Dana-Farber Cancer Institute
9 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 and Herceptin in people with Breast Cancer, run by Nancy Lin, MD at 9 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 14 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 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 15 Mar 2022). 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?
Objective Response Rate (time frame: 8 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 NCT00470704, which also lists 1 linked publication.
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 Dec 2024.