Lapatinib In Combination With Chemotherapy In Subjects With Relapsed Breast Cancer
This study has been terminated.
(Study was terminated due to difficulty in identifying eligible subjects)
Information provided by (Responsible Party):
First received: May 25, 2007
Last updated: May 31, 2012
Last verified: June 2011
This study will evaluate the safety and efficacy of lapatinib in combination with chemotherapy (capecitabine, docetaxel, nab-paclitaxel) in subjects with ErbB2-overexpressing breast cancer whose disease has progressed during or within 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.
Relapsed Breast Cancer
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||An Open-label, Multi-centre Study of Lapatinib in Combinationwith Chemotherapy in Patients With ErbB2 Overexpressing Breastcancer After Trastuzumab Failure in the Neoadjuvant or Adjuvantsetting.
Primary Outcome Measures:
Secondary Outcome Measures:
- Clinical Benefit (CB) [ Time Frame: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason) ] [ Designated as safety issue: No ]
CB is defined as the percentage of participants (par.) with either a confirmed CR or PR or stable disease (SD) for at least 24 weeks. SD is defined as small changes that do not meet criteria for CR, PR, or Progressive Disease (defined as at least a 20% increase in the sum of the longest diameter of target lesions).
- Duration of Response [ Time Frame: time from first documented evidence of CR or PR until the first documented sign of disease progression or death (approximately 95 weeks) ] [ Designated as safety issue: No ]
For the subset of participants with a confirmed CR or PR, duration of response was measured as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
- Time to Response (TTR) [ Time Frame: start of treatment until first documented evidence of CR or PR (approximately 95 weeks) ] [ Designated as safety issue: No ]
TTR is defined as the time from the start of treatment until the first documented evidence of PR or CR (whichever status was recorded first). When tumor response was confirmed at a repeat assessment, the TTR was taken to be the first time that the response was observed.
- Progression-free Survival [ Time Frame: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks); dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason) ] [ Designated as safety issue: No ]
The time from the start of treatment until the earliest date of disease progression or death due to any cause was measured.
- Number of Participants With the Indicated Serious Adverse Events and Adverse Events [ Time Frame: Baseline through End of Treatment, or discontinuation of study therapy (approximately 95 weeks); from the first dose of lapatinib until 5 days after the last dose of lapatinib ] [ Designated as safety issue: No ]
Qualitative and quantitative toxicities associated with the combination of capecitabine, docetaxel, or nab-paclitaxel and lapatinib were measured. Data are presented as serious adverse events (SAEs) and adverse events (AEs). See the SAE/AE section of the results record for data.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||September 2009 (Final data collection date for primary outcome measure)
Experimental: Lapatinib plus Chemotherapy
Lapatinib is administered in combination with one of the following chemotherapies based on the discretion of the investigator : capecitabine, docetaxel or nab-paclitaxel.
Small molecule tyrosine kinase inhibitor
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Signed informed consent.
- Histologically/cytologically confirmed breast cancer;
If the disease is restricted to a solitary lesion, the neoplastic nature of the lesion must be confirmed by cytology or histology.
- Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors) [Therasse, 2000].
- Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) or documented overexpression of the ErbB2 protein by 3+ IHC in primary or metastatic tumor tissue.
- Subjects must have relapsed breast cancer where the disease progressed during or ≤ 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.
Note: Progression is defined using RECIST criteria, that is, either the appearance of new lesions or a >=20% increase in the sum of longest diameter (LD).
- Subjects must not have received prior anti-cancer therapy for metastatic breast cancer (MBC). Subjects who received prior antihormonal agents combined with trastuzumab for the treatment of disease which first presented as ER positive MBC and recurred while receiving trastuzumab or ≤ 3 months after completing this therapy are eligible.
- Subjects with stable central nervous system (CNS) metastases as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI) are allowed. Treatment with prophylactic anticonvulsants is permitted, unless listed within the Prohibited Medications.
- Subjects must have a baseline cardiac ejection fraction (LVEF) ³50% measured by echocardiogram (ECHO) (or multigated acquisition (MUGA) scan if an ECHO cannot be performed). The same modality used at baseline must be used for repeat assessment throughout study. Only subjects with controlled or asymptomatic angina or arrhythmias are eligible.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
- Subjects must have archived tumor tissue from the initial diagnosis available for analysis. If tissue from the initial diagnosis is not available, then tissue must be obtained from a recurrent or metastatic site prior to initiating study treatment.
- Female ≥18 years.
- Subject must have adequate organ function as defined in Table 1.
- Table 1: Baseline Laboratory Values for Adequate Organ Function.
Absolute neutrophil count: ≥1.5 X 10^9/L
Hemoglobin: ≥9 g/dL
Platelets: ≥ 75 X 10^9/L
AST, ALT and Alkaline phosphatase: ≤ 2.5 X ULN
Unless concomitant docetaxel, then ≤ 1.5 x ULN for AST and ALT, with AP ≤ 2.5 x ULN
Unless documented liver metastasis, then ≤ 5 x ULN
Serum bilirubin: ≤ 2.0 X ULN
Albumin: ≥ 2.5 g/dL
Serum Creatinine: ≤ 1.5 mg/dL
- Pregnant or lactating females.
- Women of childbearing potential who do not practice approved contraceptive methods (for example, intrauterine device [IUD], birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product.
- 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 therapy given to treat cancer (chemotherapy, radiation therapy, immunotherapy, biologic therapy, anti-hormonal therapy) while taking study medication.
- Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
- Malabsorption syndrome or resection of the stomach or small bowel significantly affecting gastrointestinal function.
- Have current active haptic or biliary disease (with excpetion of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
- Concurrent disease or condition that, in the opinion of the physician, would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety (for example, uncontrolled infection, or any psychiatric condition prohibiting understanding or rendering of informed consent).
- Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents for anti-cancer therapy.
- Bisphosphonates may not be initiated after the first dose of study medication.
- Considered by the Investigator to have a life expectancy less than 3 months.
- Not able to swallow or retain oral medication.
- The subject with a known unmanageable hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients and those related to capecitabine, docetaxel, nab paclitaxel or their excipients.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00479856
||GSK Clinical Trials
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 25, 2007
|Results First Received:
||May 3, 2010
||May 31, 2012
||United States: Food and Drug Administration
Keywords provided by GlaxoSmithKline:
Relapsed breast cancer
dual tyrosine kinase inhibitor
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 16, 2015
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors