Lapatinib In Combination With Trastuzumab Versus Lapatinib Monotherapy In Subjects With HER2-positive Metastatic Breast Cancer

NCT ID: NCT00320385

Last Updated: 2016-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 296 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2010-10-31

Brief Summary

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.

Conditions

Neoplasms, Breast

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Lapatinib plus Trastuzumab

Lapatinib 1000mg once daily in combination with trastuzumab 4mg/kg loading dose followed by 2mg/kg weekly

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

oral lapatinib once daily

Trastuzumab

Intervention Type: BIOLOGICAL

IV trastuzumab 2mg/kg weekly after 4mg/kg loading dose

Arm 2: Lapatinib

Lapatinib 1500mg once daily

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

oral lapatinib once daily

Interventions

Lapatinib

oral lapatinib once daily

Intervention Type: DRUG

Trastuzumab

IV trastuzumab 2mg/kg weekly after 4mg/kg loading dose

Intervention Type: BIOLOGICAL

Other Intervention Names

Tyverb; Tykerb; Herceptin

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Sedona, Arizona, United States

GSK Investigational Site

Highland, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

Santa Rosa, California, United States

GSK Investigational Site

Vallejo, California, United States

GSK Investigational Site

Newark, Delaware, United States

GSK Investigational Site

Boca Raton, Florida, United States

GSK Investigational Site

Fort Myers, Florida, United States

GSK Investigational Site

Gainesville, Florida, United States

GSK Investigational Site

Hollywood, Florida, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Ocala, Florida, United States

GSK Investigational Site

Ocoee, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

West Palm Beach, Florida, United States

GSK Investigational Site

Lawrenceville, Georgia, United States

GSK Investigational Site

Niles, Illinois, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Terre Haute, Indiana, United States

GSK Investigational Site

Cedar Rapids, Iowa, United States

GSK Investigational Site

Kansas City, Kansas, United States

GSK Investigational Site

Overland Park, Kansas, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Minneapolis, Minnesota, United States

GSK Investigational Site

Robbinsdale, Minnesota, United States

GSK Investigational Site

Columbia, Missouri, United States

GSK Investigational Site

Saint Joseph, Missouri, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Montclair, New Jersey, United States

GSK Investigational Site

Morristown, New Jersey, United States

GSK Investigational Site

New Brunswick, New Jersey, United States

GSK Investigational Site

Summit, New Jersey, United States

GSK Investigational Site

Voorhees Township, New Jersey, United States

GSK Investigational Site

Albany, New York, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Cary, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Durham, North Carolina, United States

GSK Investigational Site

Hickory, North Carolina, United States

GSK Investigational Site

Canton, Ohio, United States

GSK Investigational Site

Kettering, Ohio, United States

GSK Investigational Site

Oklahoma City, Oklahoma, United States

GSK Investigational Site

Tulsa, Oklahoma, United States

GSK Investigational Site

Bryn Mawr, Pennsylvania, United States

GSK Investigational Site

Hershey, Pennsylvania, United States

GSK Investigational Site

Kingston, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

West Reading, Pennsylvania, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

Arlington, Texas, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Beaumont, Texas, United States

GSK Investigational Site

Bedford, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Denton, Texas, United States

GSK Investigational Site

El Paso, Texas, United States

GSK Investigational Site

Fort Worth, Texas, United States

GSK Investigational Site

Fredericksburg, Texas, United States

GSK Investigational Site

Lewisville, Texas, United States

GSK Investigational Site

Longview, Texas, United States

GSK Investigational Site

McAllen, Texas, United States

GSK Investigational Site

Mesquite, Texas, United States

GSK Investigational Site

Midland, Texas, United States

GSK Investigational Site

Odessa, Texas, United States

GSK Investigational Site

Paris, Texas, United States

GSK Investigational Site

Tyler, Texas, United States

GSK Investigational Site

Waco, Texas, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Salem, Virginia, United States

GSK Investigational Site

Edmonds, Washington, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Spokane, Washington, United States

GSK Investigational Site

Vancouver, Washington, United States

GSK Investigational Site

Yakima, Washington, United States

GSK Investigational Site

Green Bay, Wisconsin, United States

GSK Investigational Site

Salzburg, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Laval, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Split, , Croatia

GSK Investigational Site

Zagreb, , Croatia

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Tampere, , Finland

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, Germany

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, Germany

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, Germany

GSK Investigational Site

Augsburg, Bavaria, Germany

GSK Investigational Site

Coburg, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Fürstenwalde, Brandenburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Leer, Lower Saxony, Germany

GSK Investigational Site

Herne, North Rhine-Westphalia, Germany

GSK Investigational Site

Troisdorf, North Rhine-Westphalia, Germany

GSK Investigational Site

Velbert, North Rhine-Westphalia, Germany

GSK Investigational Site

Saarbrücken, Saarland, Germany

GSK Investigational Site

Halle, Saxony-Anhalt, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Kiel, Schleswig-Holstein, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Neo Faliro, , Greece

GSK Investigational Site

Bari, Apulia, Italy

GSK Investigational Site

Lecce, Apulia, Italy

GSK Investigational Site

Ravenna, Emilia-Romagna, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Rozzano (MI), Lombardy, Italy

GSK Investigational Site

Perugia, Umbria, Italy

GSK Investigational Site

Bialystok, , Poland

GSK Investigational Site

Olsztyn, , Poland

GSK Investigational Site

Olsztyn, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Wroclaw, , Poland

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Hospitalet de Llobregat (Barcelona), , Spain

GSK Investigational Site

Lleida, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Santa Cruz de Tenerife, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Huddersfield, , United Kingdom

GSK Investigational Site

Ipswich, , United Kingdom

GSK Investigational Site

London, , United Kingdom

Countries

United States; Austria; Bulgaria; Canada; Croatia; Czechia; Finland; Germany; Greece; Italy; Poland; Spain; United Kingdom

References

Wu Y, Amonkar MM, Sherrill BH, O'Shaughnessy J, Ellis C, Baselga J, Blackwell KL, Burstein HJ. 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 Dec;22(12):2582-2590. doi: 10.1093/annonc/mdr014. Epub 2011 Mar 15.

Reference Type: BACKGROUND

PMID: 21406472 (View on PubMed)

Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, 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 human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012 Jul 20;30(21):2585-92. doi: 10.1200/JCO.2011.35.6725. Epub 2012 Jun 11.

Reference Type: BACKGROUND

PMID: 22689807 (View on PubMed)

Other Identifiers

EGF104900

Identifier Type: -

Identifier Source: org_study_id