Last updated: 11/04/2018 06:26:24
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
Lapatinib In Combination With Trastuzumab Versus Lapatinib Monotherapy In Subjects With HER2-positive Metastatic Breast Cancer
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: A Randomized, Multicenter, Open-Label, Phase III Study of Lapatinib in Combination with Trastuzumab versus Lapatinib Monotherapy in Subjects with HER2-positive Metastatic Breast Cancer whose disease has progressed on Trastuzumab-Containing Regimens
Trial description: This study will evaluate and compare the safety and efficacy of lapatinib in combination with trastuzumab versus lapatinib monotherapy in subjects with HER2-positive metastatic breast cancer.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Progression-Free Survival (PFS)
Timeframe: Baseline to disease progression or death due to any cause or 30 days after last dose (up to 216 weeks)
Secondary outcomes:
Overall Survival (OS)
Timeframe: Baseline to death or 30 days after last dose for the last participant (up to 216 weeks)
Overall Tumor Response (OR)
Timeframe: Baseline to disease progression or death or discontinuation from study or 30 days after last dose (up to 216 weeks)
Clinical Benefit Response (CBR)
Timeframe: Baseline to disease progression or death or discontinuation from study or 30 days after last dose (up to 216 weeks)
Time to Response (TTR)
Timeframe: Baseline until first documented evidence of CR or PR or 30 days after last dose (up to 216 weeks)
Duration of Response (DR)
Timeframe: Time from first documented evidence of CR or PR until the first documented sign of disease progression or death or 30 days after last dose (up to 216 weeks)
Time to Progression (TTP)
Timeframe: Baseline to disease progression or death or 30 days after last dose (up to 216 weeks)
Change from Baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B) scores at Week 4, Week 12, Week 16, Week 24, and conclusion or withdrawal from study
Timeframe: Baseline, Week 4, Week 12, Week 16, Week 24, and conclusion or withdrawal from study (up to Week 108)
Interventions:
Drug: Lapatinib
Biological/vaccine: Trastuzumab
Enrollment:
296
Observational study model:
Not applicable
Primary completion date:
2007-29-06
Time perspective:
Not applicable
Clinical publications:
Wu Y, Amonkar M, Sherrill B, Ellis C. Impact of Lapatinib Plus Trastuzumab Versus Single-Agent Lapatinib on Quality of Life of Patients With Trastuzumab-Refractory HER2+ Metastatic Breast Cancer. [Ann Oncol]. 2011;
Blackwell K, Burstein H, Storniolo A, Rugo H, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Overall Survival Benefit with Lapatinib in Combination with Trastuzumab for Patients with HER2-Positive Metastatic Breast Cancer: Final Results from the EGF104900 Study. [J Clin Oncol]. 2012;
Medical condition
Neoplasms, Breast
Product
lapatinib
Collaborators
Not applicable
Study date(s)
November 2005 to October 2010
Type
Interventional
Phase
3
Participation criteria
Sex
Female
Age
18+ years
Accepts healthy volunteers
No
- Signed informed consent.
- Female ≥18 years. Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, if appropriate (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.
- Pregnant or lactating females.
- Prior therapy with an ErbB1 and/or ErbB2 inhibitor other than trastuzumab.
Inclusion and exclusion criteria
Inclusion criteria:
- Signed informed consent.
- Female ≥18 years. Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, if appropriate (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.
- Metastatic breast cancer, histologically/cytologically confirmed. If the disease is restricted to a solitary lesion, its neoplastic nature must be confirmed by cytology or histology.
- Subjects must have stage IV breast cancer whereby their disease has progressed in either the adjuvant or metastatic setting. 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 must have documented progression following at least ONE trastuzumab plus cytotoxic chemotherapy or anti-hormonal regimen in the metastatic setting.
- Note: The most recent treatment must have contained trastuzumab, either alone or in combination with other therapy in the metastatic setting, and subjects must have progressed while on this regimen. Progression is defined as either new lesions or a ≥20% increase in the sum of longest diameter (LD) on the progression radiologic scan.
- Subjects must have archived tumor tissue available for testing.
- Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) or documented overexpression of the ErbB2 protein by IHC in primary or metastatic tumor tissue. The IHC or FISH amplification may be documented by a local or central laboratory for randomization into the study. Subjects may be randomized on the basis of ErbB2 positivity by IHC 3+ overexpression or FISH amplification.
- Lesion eligibility is as follows:
- at least one measurable lesion(s) according to Response Evaluation Criteria in Solid Tumors [RECIST; Therasse, 2000], or
- bone-only disease.
- Note: Tumor lesions which are situated in a previously irradiated field, and have well-defined margins which are located in soft tissue will be defined as measurable disease.
- Subjects with stable CNS metastases defined as asymptomatic and off systemic steroids and anticonvulsants for at least 1 month. Treatment with prophylactic anticonvulsants is permitted, unless listed within the Prohibited Medications (Section 8.2).
- Radiotherapy if received within 2 weeks prior to initiation of investigational product to a limited area (e.g., palliative treatment for painful disease) other than the sole site of measurable disease is allowed; however, subject must have completed treatment and recovered from all treatment-related toxicities prior to administration of the first dose of investigational product.
- With the single exception of prior trastuzumab treatment, all prior chemotherapy, immunotherapy, biologic therapy, or surgery (except for minor surgical procedures) must be discontinued at least 3 weeks prior to the first dose of investigational product. Subjects must have recovered or stabilized sufficiently from treatment-related toxicities prior to administration of the first dose of investigational product.
- Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of investigational product. Prophylactic use of bisphosphonates is permitted only for the treatment of osteoporosis.
- ECOG Performance Status of 0 to 2.
- Able to swallow and retain oral medication.
- 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. Same modality used at baseline must be used for repeat assessments throughout study.
- Subject must have adequate organ function as defined in Table 1 :
- Table 1 (Definitions for Adequate Hematologic and Hepatic Function)
- SYSTEM (LABORATORY VALUES)
- Hematologic:
- ANC (absolute neutrophil count) (≥ 1x10^9/ L)
- Hemoglobin (≥ 9 g / dL)
- Platelets (≥75x10^9/ L)
- Hepatic
- Albumin (≥ 2.5 g / dL)
- Serum bilirubin (≤ 2 mg / dL)
- AST and ALT (≤ 3 x ULN without liver metastases) (≤ 5 xULN if documented liver metastases)
- Renal
- Serum Creatinine (≤1.5 mg / dL)
- OR
- Calculated Creatinine Clearance1 (≥40 mL / min)
- Calculated by the Cockcroft and Gault Method.
- Subjects may continue anti-estrogen therapy only if treatment was initiated at least 1 month prior to the first dose of investigational product (IP). After randomization, no anti-hormonal therapy may be initiated.
Exclusion criteria:
- Pregnant or lactating females.
- Prior therapy with an ErbB1 and/or ErbB2 inhibitor other than trastuzumab.
- 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.
- Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
- 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, arrhythmias, or congestive heart failure.
- Known history or clinical evidence of leptomeningeal carcinomatosis.
- Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy).
- Concurrent treatment with an investigational agent or participation in another clinical trial.
- Used an investigational drug within 3 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational product.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or their excipients.
- Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
Trial location(s)
Location
GSK Investigational Site
Lewisville, Texas, United States, 75067
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39108
Status
Study Complete
Location
GSK Investigational Site
Fredericksburg, Texas, United States, 78624
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Albany, New York, United States, 12208
Status
Study Complete
Location
GSK Investigational Site
Durham, North Carolina, United States, 27710
Status
Study Complete
Location
GSK Investigational Site
Hershey, Pennsylvania, United States, 17033
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boca Raton, Florida, United States, 33428
Status
Study Complete
Location
GSK Investigational Site
Green Bay, Wisconsin, United States, 54301
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Greenville, South Carolina, United States, 29605
Status
Study Complete
Location
GSK Investigational Site
Spokane, Washington, United States, 99202
Status
Study Complete
Location
GSK Investigational Site
Overland Park, Kansas, United States, 66210
Status
Study Complete
Location
GSK Investigational Site
Hospitalet de Llobregat (Barcelona), Spain, 08907
Status
Study Complete
Location
GSK Investigational Site
Summit, New Jersey, United States, 07901
Status
Study Complete
Location
GSK Investigational Site
Fuerstenwalde, Brandenburg, Germany, 15517
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
Status
Study Complete
Location
GSK Investigational Site
Santa Rosa, California, United States, 95403-1757
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69115
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85012
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Cedar Rapids, Iowa, United States, 52403
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Voorhees, New Jersey, United States, 08043
Status
Study Complete
Location
GSK Investigational Site
San Francisco, California, United States, 94115-1710
Status
Study Complete
Location
GSK Investigational Site
Saarbruecken, Saarland, Germany, 66113
Status
Study Complete
Location
GSK Investigational Site
Herne, Nordrhein-Westfalen, Germany, 44623
Status
Study Complete
Location
GSK Investigational Site
Highland, California, United States, 92346
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Tulsa, Oklahoma, United States, 74136-1902
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
Status
Study Complete
Location
GSK Investigational Site
Lawrenceville, Georgia, United States, 30046-7650
Status
Study Complete
Location
GSK Investigational Site
Sedona, Arizona, United States, 86336
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Las Vegas, Nevada, United States, 89109
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Augsburg, Bayern, Germany, 86150
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Fort Worth, Texas, United States, 76104
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Diego, California, United States, 92120
Status
Study Complete
Location
GSK Investigational Site
Muenchen, Bayern, Germany, 80331
Status
Terminated/Withdrawn
Location
GSK Investigational Site
St. Joseph, Missouri, United States, 64507
Status
Study Complete
Location
GSK Investigational Site
Gainesville, Florida, United States, 32605
Status
Study Complete
Location
GSK Investigational Site
Santa Cruz de Tenerife, Spain, 38320
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Longview, Texas, United States, 75601
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New York, New York, United States, 10016
Status
Study Complete
Location
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70199
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Waco, Texas, United States, 76712
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Montreal, Québec, Canada, H4J 1C5
Status
Terminated/Withdrawn
Location
GSK Investigational Site
West Reading, Pennsylvania, United States, 19611
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hollywood, Florida, United States, 33021
Status
Study Complete
Location
GSK Investigational Site
Vallejo, California, United States, 94589
Status
Study Complete
Location
GSK Investigational Site
Terre Haute, Indiana, United States, 47802
Status
Study Complete
Location
GSK Investigational Site
Morristown, New Jersey, United States, 07962
Status
Study Complete
Location
GSK Investigational Site
Jacksonville, Florida, United States, 32256
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73112
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24103
Status
Study Complete
Location
GSK Investigational Site
Las Vegas, Nevada, United States, 89135
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Robbinsdale, Minnesota, United States, 55422
Status
Study Complete
Location
GSK Investigational Site
Beaumont, Texas, United States, 77702-1449
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Charlotte, North Carolina, United States, 28203
Status
Study Complete
Location
GSK Investigational Site
Troisdorf, Nordrhein-Westfalen, Germany, 53840
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23230
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Orlando, Florida, United States, 32804
Status
Study Complete
Location
GSK Investigational Site
Seattle, Washington, United States, 98133
Status
Study Complete
Location
GSK Investigational Site
Vancouver, Washington, United States, 98684
Status
Study Complete
Location
GSK Investigational Site
Columbia, Missouri, United States, 65201
Status
Study Complete
Location
GSK Investigational Site
Kingston, Pennsylvania, United States, 18704
Status
Study Complete
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55404
Status
Study Complete
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46227
Status
Study Complete
Location
GSK Investigational Site
Velbert, Nordrhein-Westfalen, Germany, 42551
Status
Study Complete
Location
GSK Investigational Site
Ocoee, Florida, United States, 34761
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dallas, Texas, United States, 75237
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Halle, Sachsen-Anhalt, Germany, 06120
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bedford, Texas, United States, 76022
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Arlington, Texas, United States, 76014
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kettering, Ohio, United States, 45409
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hickory, North Carolina, United States, 28602
Status
Study Complete
Location
GSK Investigational Site
Edmunds, Washington, United States, 98026
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Montclair, New Jersey, United States, 07042
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Cary, North Carolina, United States, 27511
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ocala, Florida, United States, 34474
Status
Terminated/Withdrawn
Location
GSK Investigational Site
West Palm Beach, Florida, United States, 33401
Status
Study Complete
Location
GSK Investigational Site
Newark, Delaware, United States, 19713
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Location
GSK Investigational Site
McAllen, Texas, United States, 78503-1298
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70190
Status
Study Complete
Location
GSK Investigational Site
Norfolk, Virginia, United States, 23502
Status
Study Complete
Location
GSK Investigational Site
Mesquite, Texas, United States, 75150
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bryn Mawr, Pennsylvania, United States, 19010
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02115
Status
Study Complete
Location
GSK Investigational Site
Fort Myers, Florida, United States, 33916
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95819
Status
Study Complete
Location
GSK Investigational Site
Yakima, Washington, United States, 98902
Status
Study Complete
Location
GSK Investigational Site
Kansas City, Kansas, United States, 66103
Status
Study Complete
Location
GSK Investigational Site
New Brunswick, New Jersey, United States, 08901
Status
Terminated/Withdrawn
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
No longer a GSK study
Actual primary completion date
2007-29-06
Actual study completion date
2010-29-10
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.
Additional information about the trial
Additional information
Not applicable
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Access to clinical trial data by researchers
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