Last updated: 07/17/2024 15:06:01
Capecitabine (XELODA) With Or Without Lapatinib (GW572016) For Women With Refractory Advanced or Metastatic Breast Cancer
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase III, Randomized, Open-label, Multicenter Study Comparing GW572016 and Capecitabine (XELODA) versus Capecitabine in Women with Refractory Advanced or Metastatic Breast Cancer
Trial description: This study was designed to compare the efficacy and safety of an oral dual tyrosine kinase inhibitor in combination with capecitabine versus capecitabine alone in women with locally advanced or metastatic breast cancer that has not responded to previous therapy.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Median time to progression based on radiological imaging data as per independent review committee (IRC)
Timeframe: From Day 1 (randomization) till disease progression or death whichever occurs the first, assessed up to approximately 2 years
Secondary outcomes:
Overall survival over period
Timeframe: From Day 1 (randomization) through end of study (approximately up to 6 years)
Progression-free survival over period
Timeframe: From Day 1 (randomization) till disease progression or death whichever occurs the first, assessed up to approximately 2 years
Percentage of participants achieving complete response (CR) or partial response (PR ) for assessing the overall tumor response rate (ORR) over period
Timeframe: Approximately up to 2 years
Clinical benefit rate (CBR) over period
Timeframe: Approximately up to 2 years
Time to response over period
Timeframe: From Day 1 (randomization) up to 36 weeks
Duration of response over period
Timeframe: From Day 1 (randomization) till disease progression or death whichever occurs the first, assessed up to approximately 2 years
Number of participants with toxicity grades for hematological parameters at any visit post screening
Timeframe: Approximately up to 2 years
Number of participants with toxicity grades of clinical chemistry parameters at any visit post screening
Timeframe: Approximately up to 2 years
Number of participants with electrocardiogram (ECG) findings over period
Timeframe: Approximately up to 2 years
Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) over period
Timeframe: Baseline (Day 1, pre-dose) up to Week 84
Change from Baseline in heart rate over period
Timeframe: Baseline (Day 1, pre-dose) up to Week 84
Mean change from Baseline in body temperature over period
Timeframe: Baseline (Day 1, pre-dose) up to Week 72
Change from Baseline in body weight over period
Timeframe: Baseline (Day 1, pre-dose) up to Week 84
Percentage of participants with absolute change from Baseline in left ventricular ejection fraction over period
Timeframe: Baseline (Day 1) up to Week 84
Number of participants with adverse events, death and serious adverse events
Timeframe: Approximately up to 2 years
Change from Baseline in Quality of Life (QOL) over period
Timeframe: Approximately up to 2 years
Change from Baseline in tumor genetic analysis factors (mutations, copy number, variability and expression levels)
Timeframe: Approximately up to 2 years
Change from Baseline in Biomarkers (EGFR, HER-2/neu, and other downstream biomarkers)
Timeframe: Approximately up to 2 years
Interventions:
Enrollment:
408
Primary completion date:
2006-21-04
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. doi: 10.1634/theoncologist.2009-0181. Epub 2010 Aug 24.
Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. doi: 10.1007/s10549-007-9885-0. Epub 2008 Jan 11.
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. Erratum in: N Engl J Med. 2007 Apr 5;356(14):1487.
Toi M, Iwata H, Fujiwara Y, Wakamatsu T, Kanezaki M, Katsura K, Koehler M, Ellis C, Gagnon R, Allen K, Sasaki Y, Takashima S . Efficacy, Safety and Biomarker Findings in Patients with Advanced or Metastatic Breast Cancer Treated with Lapatinib Monotherapy: Results from 122 Japanese Patients Treated in 2 Phase II Studies. [Br J Cancer]. 2009;101(10):1676-1682.
Zhou X, Segreti A, Cella D, Cameron D, Geyer C, Amonkar M, Stein S, Walker M. Lapatinib plus capecitabine versus capecitabine alone for HER2+ metastatic breast cancer: quality of life assessment. [Breast Cancer Res Treat]. 2009;DOI 10.1007/S10549-009-03(Jan online):
Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer C. Lapatinib Plus Capecitabine in Women With HER2-Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial. Oncologist. 2010;15:924-34.
Delea TE, Tappenden P, Sofrygin O, Browning D, Amonkar M, Karnon J, Walker MD, Cameron D. Cost-Effectiveness of Lapatinib plus Capecitabine in Women with HER2+ Metastatic Breast Cancer who Have Received Prior Therapy with Trastuzumab. Eur J Health Econ. 2012;13(5):589-603.
Zhou X, Segreti A, Cella D, Cameron D, Geyer C, Amonkar M, Stein S, Walker M. Lapatinib plus capecitabine versus capecitabine alone for HER2+ metastatic breast cancer: quality of life assessment. Breast Cancer Res Treat. 2009;DOI 10.1007/S10549-009-03(Jan online):
Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. NEJM. 2006;355:2733-2743.
Medical condition
Neoplasms, Breast
Product
lapatinib
Collaborators
Not applicable
Study date(s)
March 2004 to February 2010
Type
Interventional
Phase
3
Participation criteria
Sex
Female
Age
18+ years
Accepts healthy volunteers
No
- Signed informed consent
- Patients must have histologically confirmed invasive breast cancer with stage IIIb, stage IIIc with T4 lesion, or stage IV disease
- Pregnant or lactating females at anytime during the study
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are also excluded
Inclusion and exclusion criteria
Inclusion criteria:
- Signed informed consent
- Patients must have histologically confirmed invasive breast cancer with stage IIIb, stage IIIc with T4 lesion, or stage IV disease
- Documentation of ErbB2 overexpression (immunohistochemistry (IHC) 3+ or IHC 2+ with fluorescence in situ hybridization (FISH) confirmation) is required based on local laboratory or initial diagnostic results. Where testing is not feasible, central laboratory testing will be utilized
- Subjects must have documented progressive advanced or metastatic breast cancer. Progression for entry is defined as appearance of any new lesion not previously identified or increase of 25% or more in existent lesions and must be documented
- Subjects must have refractory breast cancer defined as progression in the locally advanced or metastatic setting or relapse within 6 months of completing adjuvant therapy. Prior therapies must include, but are not limited to: ·Taxane containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on taxane ·Anthracycline containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on anthracycline ·Subjects who relapse > 6 months after completion of adjuvant anthracycline-containing chemotherapy, and for whom further anthracycline is not indicated, will be considered to have met the anthracycline prior exposure requirement ·Taxanes and Anthracyclines may have been administered concurrently or separately ·Prior treatment with capecitabine is not permitted
- Prior treatment must have contained trastuzumab (Herceptin) alone or in combination with other chemotherapy for at least 6 weeks of standard doses in the locally advanced or metastatic setting. Trastuzumab administered in the adjuvant setting is not exclusionary, but for eligibility trastuzumab must also have been administered in the locally advanced or metastatic setting.
- Subjects with hormone receptor positive tumors must have disease progression following hormonal therapy unless intolerant to hormonal therapy or hormonal therapy is not considered to be clinically appropriate
- Subjects with stable central nervous system (CNS) metastases (asymptomatic and off systemic steroids and anticonvulsants for at least 3 months) are eligible
- Female subjects must be≥18 years of age
- Eastern Cooperative Oncology Group (ECOG Performance Status of 0 or 1
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
- Subjects must have archived tumor tissue available to re-evaluate intra-tumoral expression levels of ErbB1 and ErbB2 by IHC and FISH testing performed by the study central laboratory. Central laboratory results will not be used to determine subject eligibility for the study, unless testing is being used for required documentation of ErbB2 overexpression.
- Life expectancy of ≥12 weeks
- Subjects must have recovered from clinically significant side effects associated with prior radiotherapy and chemotherapy
- Measurable lesions may be in the field of prior irradiation. However, there must be at least a 4-week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable
- Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram (multigated acquisition (MUGA) scan may be performed if ECHO is not available)
- Able to swallow and retain oral medication
- Subjects must complete all screening assessments as outlined in the protocol
- Adequate renal function defined as a Creatinine Clearance ≥50mL/min, determined by calculated creatinine clearance using Cockcroft and Gault Method and normalized to Body Surface Area (BSA)
- Adequate hematologic and hepatic function as defined in Table 1: Table 1 (Body System and Adequate Function Definitions) SYSTEM (LABORATORY VALUES) Hematologic: ANC (absolute neutrophil count) ≥1.5 x 10^9/L Hemoglobin ≥9 g/dL Platelets ≥100 x 10^9/L Hepatic: Albumin ≥2.5 g/dL Serum bilirubin ≤1.5 x upper limit of normal (ULN) ≤2.5 x ULN if patient has Gilbert’s syndrome aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN without liver metastases ≤5 x ULN if documented liver metastases
Exclusion criteria:
- Pregnant or lactating females at anytime during the study
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are also excluded
- History of other malignancy. 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
- Unresolved or unstable serious toxicity from prior administration of another investigational drug
- Active or uncontrolled infection
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
- Known history of uncontrolled or symptomatic angina, arrhythmia or congestive heart failure
- No prior anti-ErbB1/ErbB2 inhibitor for breast cancer other than trastuzumab
- Known history or clinical evidence of leptomeningeal carcinomatosis
- Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than capecitabine
- Bisphosphonates for the treatment of bone metastases should not be initiated following the first dose of randomized therapy. Prophylactic use of bisphosphonates in subjects without bone disease is not permitted, except for prevention of osteoporosis
- Concurrent treatment with an investigational agent or participation in another clinical trial
- Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GW572016 or excipients of GW572016
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to capecitabine, fluorouracil or any excipients
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
Trial location(s)
Location
GSK Investigational Site
Albany, New York, United States, 12208
Status
Study Complete
Location
GSK Investigational Site
Annapolis, Maryland, United States, 21401
Status
Study Complete
Location
GSK Investigational Site
Athlone Park, Amanzimtoti, South Africa, 4126
Status
Study Complete
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Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2006-21-04
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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