Lapatinib +Capecitabine Treatment for Advanced Metastatic Breast Cancer in Women From China
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: lapatinib in combination with capecitabine daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000mg/m2/day on days1-14 every 21 days) |
Drug: lapatinib
Lapatinib ditosylate monohydrate tablets, 250 mg, are oval, biconvex, orange, film-coated tablets taken orally.
Other Names:
Drug: capecitabine
Capecitabine is supplied as a biconvex, oblong, light peach and peach colored, film-coated tablets for oral administration.
|
Outcome Measures
Primary Outcome Measures
- Clinical Benefit Rate (CBR) [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.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [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.]
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.
- Six Months Progression-Free Survival [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.]
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.
- Time to Response (TTR) [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]
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.
- Duration of Response (DOR) [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.]
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.
- Number of Participants With Central Nervous System (CNS) as First Site of Relapse [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]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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:
-
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
Exclusion Criteria:
-
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;
-
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;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Guangzhou | Guangdong | China | 510060 |
| 2 | Novartis Investigative Site | Guangzhou | Guangdong | China | 510515 |
| 3 | Novartis Investigative Site | Wuhan | Hubei | China | 430030 |
| 4 | Novartis Investigative Site | Nanjing | Jiangsu | China | 210009 |
| 5 | Novartis Investigative Site | Hangzhou | Zhejiang | China | 310006 |
| 6 | Novartis Investigative Site | Hangzhou | Zhejiang | China | 310022 |
| 7 | Novartis Investigative Site | Beijing | China | 100021 | |
| 8 | Novartis Investigative Site | Beijing | China | 100071 | |
| 9 | Novartis Investigative Site | Shanghai | China | 200032 | |
| 10 | Novartis Investigative Site | Hong Kong | Hong Kong | ||
| 11 | Novartis Investigative Site | Shatin | Hong Kong |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
- EGF109491
- CLAP016A2304
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Period Title: Overall Study | |
| STARTED | 52 |
| COMPLETED | 2 |
| NOT COMPLETED | 50 |
Baseline Characteristics
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Overall Participants | 52 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
48.8
(10.61)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
52
100%
|
| Male |
0
0%
|
| Race/Ethnicity, Customized (Number) [Number] | |
| Chinese |
52
100%
|
Outcome Measures
| Title | Clinical Benefit Rate (CBR) |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population: all participants who received at least one dose of investigational product |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Measure Participants | 52 |
| Number (95% Confidence Interval) [Percentage of participants] |
57.7
111%
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population: all participants who received at least one dose of investigational product |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Measure Participants | 52 |
| Median (Full Range) [Months] |
6.34
|
| Title | Six Months Progression-Free Survival |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population: all participants who received at least one dose of investigational product |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Measure Participants | 52 |
| Number (95% Confidence Interval) [Percentage of participants] |
53.55
103%
|
| Title | Time to Response (TTR) |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population: all participants who received at least one dose of investigational product. TTR only applied to participants for whom best overall response was complete response (CR) or partial response (PR) or stable disease. |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Measure Participants | 23 |
| Median (Full Range) [Months] |
4.07
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population: all participants who received at least one dose of investigational product. DOR only applied to participants for whom best overall response is complete response (CR) or partial response (PR) or stable disease (SD). |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Measure Participants | 23 |
| Median (Full Range) [Months] |
8.18
|
| Title | Number of Participants With Central Nervous System (CNS) as First Site of Relapse |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population: all participants who received at least one dose of investigational product |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Measure Participants | 52 |
| Participants with any site of relapse |
17
32.7%
|
| Participants with CNS disease as first site of relapse |
2
3.8%
|
| Title | All Collected Deaths |
|---|---|
| Description | On treatment deaths were collected from the start of treatment up to 30 days after study drug discontinuation, for a maximum duration of 4276 days (treatment duration ranged from 13 - 4246 days) for Lapatinib and 3384 days (treatment duration ranged form 8 - 3354 days) for Capecitabine. Total deaths was collected from study start to study end (LPLV). |
| Time Frame | up to 4276 days for Lapatinib/up to 3384 days for Capecitabine (on-treatment), approx. 12 years (all collected deaths) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Clinical Database Population: all treated participants |
| Arm/Group Title | Lapatinib + Capecitabine |
|---|---|
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area |
| Measure Participants | 52 |
| Total Deaths |
11
21.2%
|
| On-treatment Deaths |
2
3.8%
|
Adverse Events
| Time Frame | On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 4276 days for Lapatinib, including the 30 days safety follow- up (treatment duration ranged from 13 to 4246 days) and 3384 days for Capecitabine, including the 30 days safety follow up (treatment duration ranged from 8 to 3354 days). | |
|---|---|---|
| Adverse Event Reporting Description | AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment | |
| Arm/Group Title | Lapatinib + Capecitabine | |
| Arm/Group Description | Daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000 mg/m2/day on Days 1-14 every 21 Days); m2 = Square meter: Body Surface Area | |
All Cause Mortality |
||
| Lapatinib + Capecitabine | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/52 (3.8%) | |
Serious Adverse Events |
||
| Lapatinib + Capecitabine | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/52 (7.7%) | |
| Blood and lymphatic system disorders | ||
| Leukopenia | 1/52 (1.9%) | |
| Neutropenia | 1/52 (1.9%) | |
| Thrombocytopenia | 1/52 (1.9%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Cervix Carcinoma | 1/52 (1.9%) | |
| Vaginal Cancer Stage 0 | 1/52 (1.9%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Haemoptysis | 1/52 (1.9%) | |
Other (Not Including Serious) Adverse Events |
||
| Lapatinib + Capecitabine | ||
| Affected / at Risk (%) | # Events | |
| Total | 49/52 (94.2%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 3/52 (5.8%) | |
| Neutropenia | 7/52 (13.5%) | |
| Gastrointestinal disorders | ||
| Diarrhoea | 26/52 (50%) | |
| Mouth Ulceration | 6/52 (11.5%) | |
| Nausea | 9/52 (17.3%) | |
| Stomatitis | 5/52 (9.6%) | |
| General disorders | ||
| Asthenia | 3/52 (5.8%) | |
| Fatigue | 13/52 (25%) | |
| Pyrexia | 4/52 (7.7%) | |
| Hepatobiliary disorders | ||
| Hyperbilirubinaemia | 20/52 (38.5%) | |
| Liver Injury | 4/52 (7.7%) | |
| Investigations | ||
| Alanine Aminotransferase Increased | 4/52 (7.7%) | |
| Aspartate Aminotransferase Increased | 4/52 (7.7%) | |
| Blood Bilirubin Increased | 5/52 (9.6%) | |
| Neutrophil Count Decreased | 3/52 (5.8%) | |
| White Blood Cell Count Decreased | 4/52 (7.7%) | |
| Metabolism and nutrition disorders | ||
| Decreased Appetite | 3/52 (5.8%) | |
| Hypokalaemia | 3/52 (5.8%) | |
| Musculoskeletal and connective tissue disorders | ||
| Back Pain | 3/52 (5.8%) | |
| Psychiatric disorders | ||
| Insomnia | 3/52 (5.8%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 4/52 (7.7%) | |
| Skin and subcutaneous tissue disorders | ||
| Dermatitis Acneiform | 3/52 (5.8%) | |
| Dry Skin | 4/52 (7.7%) | |
| Palmar-Plantar Erythrodysaesthesia Syndrome | 32/52 (61.5%) | |
| Rash | 26/52 (50%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
| Name/Title | Clinical Disclosure Office |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
- EGF109491
- CLAP016A2304