Neoplasms, BreastPhase 3NCT00508274
Lapatinib +Capecitabine Treatment for Advanced Metastatic Breast Cancer in Women From China
A Phase 3 study testing lapatinib and capecitabine in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 11 sites in 2 countries.
Trial summary
Local study in China and Hong Kong to evaluate safety and efficacy in lapatinib + capecitabine in women with Human epidermal growth factor receptor 2 (HER2) positive advanced or metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- lapatinib and capecitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 18 Jul 2007to 1 Jul 2020
- Phase
- Phase 3
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent;
- Female ≥18 years;
- Pathology that has histologically confirmed invasive breast cancer with stage IIIb/c or stage IV disease;
- If recurrent disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology or histology.
- Documented overexpression of Her2 (ErbB2) of IHC 3+ or FISH positive, in primary or metastatic tumor tissue is required for enrollment into the study; by local testing or central laboratory testing determined by country of residence. NB. Approximately, 51 subjects will be enrolled in a single stage design to test for efficacy in women from China and Hong Kong. Due to the fact that trastuzumab is not commonly prescribed in China and Hong Kong, the current study allows up to 40% of subjects who are trastuzumab naïve to be enrolled.
- Prior therapies must include at minimum a taxane and/or anthracycline and may include trastuzumab if available; other prior regimens are not limited except capecitabine and Erbb2 inhibitors other than trastuzumab. Chemo regimen requirements are as follows:
Show all 27Show fewer
- Taxane containing regimen for at least 4 cycles or <4 cycles provided disease progression or treatment limiting toxicity occurred while on taxane
- Anthracycline containing regimen for at least 4 cycles or <4 cycles provided disease progression or treatment limiting toxicity occurred while on anthracycline
- Taxanes and Anthracyclines may have been administered concurrently or separately
- Prior treatment may have contained trastuzumab alone or in combination with other chemotherapy in the adjuvant, locally advanced or metastatic setting and patient must have failed the treatment
- Prior treatment with capecitabine is not permitted unless 6 months have elapsed since the last dose of capecitabine and the subject is free of any capecitabine related toxicity
- Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab is not permitted
- Other prior chemo-regimens not listed above are unlimited.
- For those subjects whose disease is ER+ and/or PR+ one of following criteria should be met.
- Subjects who received hormonal therapy and are no longer benefiting from this therapy and the hormonal treatment must have been stopped before the first dose of investigational treatment
- Subjects with visceral disease that requires chemotherapy (eg., subjects with liver or lung metastases)
- Rapidly progressing or life threatening disease, as determined by the investigator
- Subjects with stable CNS metastases (asymptomatic and off systemic steroids and anticonvulsants for at least 3 months) are eligible
- Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors);
- Radiotherapy as palliative treatment for painful metastatic disease is permitted but must have been stopped within 2 weeks prior to initiation of any investigational treatment. All subjects must have recovered from all radiotherapy related toxicities prior to initiation of any investigational treatment. The site of radiotherapy must not be used as a site of measurable disease;
- Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive;
- ECOG Performance Status of 0 to 1;
- Life expectancy of ≥ 12 weeks;
- Able to swallow and retain oral medication;
- Women with potential to have children must be willing to practice acceptable methods of birth control during the study;
- Willing to complete all screening assessments as outlined in the protocol;
- Adequate organ function as defined by the Table of Baseline Laboratory Values
Who cannot join
- Pregnant or lactating females at anytime during the study
- Subjects with only non-measurable metastatic sites of disease per RECIST, (e.g. bone metastases, pleural effusion, or ascites, etc.);
- Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment;
- Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
- History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible;
Show all 9Show fewer
- Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety;
- Uncontrolled infection;
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
China9 sites
Novartis Investigative Site
Beijing, 100021
Novartis Investigative Site
Beijing, 100071
Novartis Investigative Site
Guangzhou, Guangdong, 510060
Novartis Investigative Site
Guangzhou, Guangdong, 510515
Novartis Investigative Site
Hangzhou, Zhejiang, 310006
Novartis Investigative Site
Hangzhou, Zhejiang, 310022
Novartis Investigative Site
Nanjing, Jiangsu, 210009
Novartis Investigative Site
Shanghai, 200032
Novartis Investigative Site
Wuhan, Hubei, 430030
Hong Kong2 sites
Novartis Investigative Site
Hong Kong
Novartis Investigative Site
Shatin
About this study
Official title: An Open-Label Multicenter Study Administering Lapatinib and Capecitabine (Xeloda) in Women With Advanced or Metastatic Breast Cancer
Local study in China and Hong Kong to evaluate safety and efficacy in lapatinib + capecitabine in women with Human epidermal growth factor receptor 2 (HER2) positive advanced or metastatic breast cancer.
Read the detailed description
The Primary objective of the study was to evaluate the overall clinical benefit response (CBR) rate.
This was a single arm, open-label, multi-center study of lapatinib plus capecitabine in women from mainland China and Hong Kong who had advanced or metastatic breast cancer that progressed on prior chemotherapies with or without trastuzumab.
Participants received study treatment until disease progression, unacceptable toxicity, or withdrawal for any other reasons.
- Conditions
- Neoplasms, Breast
- Being tested
- lapatinib, capecitabine
- Keywords
- Advanced Metastatic Breast Cancer, HER2 positive, HER2+, breast cancer, lapatinib, TYVERB, TYKERB, Capecitabine
- 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 LAP016, GW572016
Lapatinib ditosylate monohydrate tablets, 250 mg, are oval, biconvex, orange, film-coated tablets taken orally.
capecitabineDrug
Capecitabine is supplied as a biconvex, oblong, light peach and peach colored, film-coated tablets for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| lapatinib in combination with capecitabine | Experimental | daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000mg/m2/day on days1-14 every 21 days) Receives: Drug: lapatinib; Drug: capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate (CBR)
CBR is defined by the percentage of participants achieving either a confirmed tumor response of complete response (CR) or partial response (PR) or stable disease (SD) for at least 24 weeks. Response Criteria in Solid Tumors (RECIST) is a system for measuring tumor shrinkage or progression in terms of the longest dimensions of the tumor on imaging scans such as computerized tomography (CT). A "partial response" requires a decrease of 30% or more, "complete response" requires all target lesions disappear, "Progression" requires an increase of at least 20%, and "Stable disease" falls in between these two. All responses have a repeat assessment to confirm the response.
Measured: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was approx. 90 months
Secondary outcomes (5)
Progression-Free Survival (PFS)
PFS is defined as the time from first dose date until the date of disease progression or death due to any reason, whichever occurs first.
Measured: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 90.38 months.
Six Months Progression-Free Survival
Six Months Progression-Free Survival is defined as the percentage of surviving participants who are progression-free longer than six months (greather than 180 days) after the first start date of study treatment.
Measured: at Baseline and every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed up to 90.38 months, with 6 months PFS reported.
Time to Response (TTR)
Time to response is defined as the time from first dose date until first documentation of disease response. TTR only applied to participants for whom best overall response was complete response (CR), partial response (PR) or stable disease (SD). Participants who had not had a partial response, complete response or stable disease at the cut-off date for this endpoint analysis were censored for time to response.
Measured: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was approx. 14.78 months
Duration of Response (DOR)
Duration of response (complete response, partial response or stable disease) is defined as the time of first documentation of disease response until the date of disease progression or death due to breast cancer, whichever occurs first. DOR only applied to participants for whom best overall response was complete response (CR), partial response (PR) or stable disease (SD). Participants who had not had a partial response, complete response or stable disease at the cut-off date for this endpoint analysis were censored for duration of response.
Measured: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 88.80 months.
Number of Participants With Central Nervous System (CNS) as First Site of Relapse
Number of participants who had Central Nervous System metastasis as the first site of relapse. CT, Magnetic Resonance Imaging, etc. were used for the assessment.
Measured: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 90 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2007 (estimated)
- Study start18 Jul 2007
- Primary completion2 Dec 2015
- Study completion1 Jul 2020
Why it stopped: Primary analysis was completed in 2015 and data collection post 1-Jul-2019 was not reportable due to local regulations in China.
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 Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00508274
- Sponsor's protocol ID
- EGF109491
- Other IDs
- CLAP016A2304
- Status last verified
- Aug 2021
- First submitted
- 26 Jul 2007
- Last updated
- 21 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Xu BH, Jiang ZF, Chua D, Shao ZM, Luo RC, Wang XJ, Liu DG, Yeo W, Yu SY, Newstat B, Preston A, Martin AM, Chi HD, Wang L. Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients. Chin J Cancer. 2011 May;30(5):327-35. doi: 10.5732/cjc.010.10507.
PubMed 21527065
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Multicenter Study Administering Lapatinib and Capecitabine (Xeloda) in Women With Advanced or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00508274
- Acronym / sponsor ID
- EGF109491
- Conditions
- Neoplasms, Breast
- Keywords
- Advanced Metastatic Breast Cancer, HER2 positive, HER2+, breast cancer, lapatinib, TYVERB, TYKERB, Capecitabine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Primary analysis was completed in 2015 and data collection post 1-Jul-2019 was not reportable due to local regulations in China.
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 18 Jul 2007 (actual)
- Primary completion
- 2 Dec 2015 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 27 Jul 2007 (estimated)
- Results
- Posted 3 Sep 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Local study in China and Hong Kong to evaluate safety and efficacy in lapatinib + capecitabine in women with Human epidermal growth factor receptor 2 (HER2) positive advanced or metastatic breast cancer.
Detailed description
The Primary objective of the study was to evaluate the overall clinical benefit response (CBR) rate.
This was a single arm, open-label, multi-center study of lapatinib plus capecitabine in women from mainland China and Hong Kong who had advanced or metastatic breast cancer that progressed on prior chemotherapies with or without trastuzumab.
Participants received study treatment until disease progression, unacceptable toxicity, or withdrawal for any other reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lapatinib in combination with capecitabine | Experimental | Drug: lapatinib, Drug: capecitabinedaily oral lapatinib (1250 mg/day) in combination with capecitabine (2000mg/m2/day on days1-14 every 21 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Signed informed consent;
- Female ≥18 years;
- Pathology that has histologically confirmed invasive breast cancer with stage IIIb/c or stage IV disease;
- Documented overexpression of Her2 (ErbB2) of IHC 3+ or FISH positive, in primary or metastatic tumor tissue is required for enrollment into the study; by local testing or central laboratory testing determined by country of residence. NB. Approximately, 51 subjects will be enrolled in a single stage design to test for efficacy in women from China and Hong Kong. Due to the fact that trastuzumab is not commonly prescribed in China and Hong Kong, the current study allows up to 40% of subjects who are trastuzumab naïve to be enrolled.
- Prior therapies must include at minimum a taxane and/or anthracycline and may include trastuzumab if available; other prior regimens are not limited except capecitabine and Erbb2 inhibitors other than trastuzumab. Chemo regimen requirements are as follows:
Key exclusion criteria (9 listed)
- Pregnant or lactating females at anytime during the study
- Subjects with only non-measurable metastatic sites of disease per RECIST, (e.g. bone metastases, pleural effusion, or ascites, etc.);
- Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment;
- Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
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: LAP016, GW572016Lapatinib ditosylate monohydrate tablets, 250 mg, are oval, biconvex, orange, film-coated tablets taken orally. | Drug | lapatinib in combination with capecitabine |
| capecitabineCapecitabine is supplied as a biconvex, oblong, light peach and peach colored, film-coated tablets for oral administration. | Drug | lapatinib in combination with capecitabine |
Primary outcome
Clinical Benefit Rate (CBR)
Time frame: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was approx. 90 months
CBR is defined by the percentage of participants achieving either a confirmed tumor response of complete response (CR) or partial response (PR) or stable disease (SD) for at least 24 weeks. Response Criteria in Solid Tumors (RECIST) is a system for measuring tumor shrinkage or progression in terms of the longest dimensions of the tumor on imaging scans such as computerized tomography (CT). A "partial response" requires a decrease of 30% or more, "complete response" requires all target lesions disappear, "Progression" requires an increase of at least 20%, and "Stable disease" falls in between these two. All responses have a repeat assessment to confirm the response.
5 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 90.38 months.
Six Months Progression-Free Survival
Time frame: at Baseline and every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed up to 90.38 months, with 6 months PFS reported.
Time to Response (TTR)
Time frame: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was approx. 14.78 months
Duration of Response (DOR)
Time frame: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 88.80 months.
Number of Participants With Central Nervous System (CNS) as First Site of Relapse
Time frame: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 90 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21527065Xu BH, Jiang ZF, Chua D, Shao ZM, Luo RC, Wang XJ, Liu DG, Yeo W, Yu SY, Newstat B, Preston A, Martin AM, Chi HD, Wang L. Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients. Chin J Cancer. 2011 May;30(5):327-35. doi: 10.5732/cjc.010.10507.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing lapatinib and capecitabine in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 11 sites in 2 countries.
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 27 inclusion and 9 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 21 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China, Hong Kong. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 3 Sep 2009). 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?
Clinical Benefit Rate (CBR) (time frame: Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was approx. 90 months). 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 NCT00508274, 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 21 Sep 2021.