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

NCT00320385 | Completed Phase 3 Results

• 1 other identifier: EGF104900
• Study Type: interventional
• Target: 296
• Locations: 13 countries
• Sites: 145

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

Keywords

lapatinib; GW572016; ErbB2; EGFR; ErbB1; MBC; FISH amplification; Metastatic Breast Cancer; dual tyrosine kinase inhibitor; Her-2/neu

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS was defined as the time from randomization until the first documented sign of disease progression or death due to any cause.

  Baseline to disease progression or death due to any cause or 30 days after last dose (up to 216 weeks)

Secondary Outcomes (7)

• Overall Survival (OS)

  Baseline to death or 30 days after last dose for the last participant (up to 216 weeks)

• Overall Tumor Response (OR)

  Baseline to disease progression or death or discontinuation from study or 30 days after last dose (up to 216 weeks)

• Clinical Benefit Response (CBR)

  Baseline to disease progression or death or discontinuation from study or 30 days after last dose (up to 216 weeks)

• Time to Response (TTR)

  Baseline until first documented evidence of CR or PR or 30 days after last dose (up to 216 weeks)

• Duration of Response (DR)

  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)

Study Arms (2)

Arm 1: Lapatinib plus Trastuzumab

EXPERIMENTAL

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

Drug: Lapatinib; Biological: Trastuzumab

Arm 2: Lapatinib

EXPERIMENTAL

Lapatinib 1500mg once daily

Drug: Lapatinib

Interventions

Lapatinib DRUG

oral lapatinib once daily

Also known as: Tyverb, Tykerb

Arm 1: Lapatinib plus Trastuzumab; Arm 2: Lapatinib

Trastuzumab BIOLOGICAL

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

Also known as: Herceptin

Arm 1: Lapatinib plus Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (145)

GSK Investigational Site

Phoenix, Arizona, 85012, United States

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GSK Investigational Site

Sedona, Arizona, 86336, United States

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Highland, California, 92346, United States

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Sacramento, California, 95819, United States

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San Diego, California, 92120, United States

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San Francisco, California, 94115-1710, United States

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Santa Rosa, California, 95403-1757, United States

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Vallejo, California, 94589, United States

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Newark, Delaware, 19713, United States

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Boca Raton, Florida, 33428, United States

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Fort Myers, Florida, 33916, United States

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Gainesville, Florida, 32605, United States

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Hollywood, Florida, 33021, United States

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Jacksonville, Florida, 32256, United States

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Miami, Florida, 33136, United States

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Ocala, Florida, 34474, United States

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Ocoee, Florida, 34761, United States

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Orlando, Florida, 32804, United States

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West Palm Beach, Florida, 33401, United States

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Lawrenceville, Georgia, 30046-7650, United States

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Niles, Illinois, 60714, United States

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Indianapolis, Indiana, 46202, United States

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Indianapolis, Indiana, 46227, United States

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Terre Haute, Indiana, 47802, United States

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Cedar Rapids, Iowa, 52403, United States

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Kansas City, Kansas, 66103, United States

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Overland Park, Kansas, 66210, United States

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Boston, Massachusetts, 02115, United States

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Minneapolis, Minnesota, 55404, United States

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Robbinsdale, Minnesota, 55422, United States

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Columbia, Missouri, 65201, United States

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Saint Joseph, Missouri, 64507, United States

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Las Vegas, Nevada, 89109, United States

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Las Vegas, Nevada, 89135, United States

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Montclair, New Jersey, 07042, United States

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Morristown, New Jersey, 07962, United States

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New Brunswick, New Jersey, 08901, United States

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Summit, New Jersey, 07901, United States

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Voorhees Township, New Jersey, 08043, United States

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Albany, New York, 12208, United States

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New York, New York, 10016, United States

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Cary, North Carolina, 27511, United States

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Charlotte, North Carolina, 28203, United States

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Durham, North Carolina, 27710, United States

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Hickory, North Carolina, 28602, United States

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Canton, Ohio, 44710, United States

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Kettering, Ohio, 45409, United States

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Oklahoma City, Oklahoma, 73112, United States

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Tulsa, Oklahoma, 74136-1902, United States

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Bryn Mawr, Pennsylvania, 19010, United States

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Hershey, Pennsylvania, 17033, United States

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Kingston, Pennsylvania, 18704, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15213, United States

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West Reading, Pennsylvania, 19611, United States

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Greenville, South Carolina, 29605, United States

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Nashville, Tennessee, 37203, United States

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Arlington, Texas, 76014, United States

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Austin, Texas, 78731, United States

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Beaumont, Texas, 77702-1449, United States

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Bedford, Texas, 76022, United States

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Dallas, Texas, 75230, United States

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Dallas, Texas, 75231, United States

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Dallas, Texas, 75237, United States

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Dallas, Texas, 75246, United States

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Denton, Texas, 76210, United States

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El Paso, Texas, 79915, United States

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Fort Worth, Texas, 76104, United States

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Fredericksburg, Texas, 78624, United States

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Lewisville, Texas, 75067, United States

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Longview, Texas, 75601, United States

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McAllen, Texas, 78503-1298, United States

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Mesquite, Texas, 75150, United States

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Midland, Texas, 79701, United States

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Odessa, Texas, 79761, United States

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Paris, Texas, 75460, United States

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Tyler, Texas, 75702, United States

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Waco, Texas, 76712, United States

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Norfolk, Virginia, 23502, United States

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Richmond, Virginia, 23230, United States

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Salem, Virginia, 24153, United States

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Edmonds, Washington, 98026, United States

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Seattle, Washington, 98133, United States

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Spokane, Washington, 99202, United States

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Vancouver, Washington, 98684, United States

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Yakima, Washington, 98902, United States

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Green Bay, Wisconsin, 54301, United States

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Salzburg, A-5020, Austria

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Vienna, A-1090, Austria

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Plovdiv, 4000, Bulgaria

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Sofia, 1572, Bulgaria

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Laval, Quebec, H7M 3L9, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Split, 21000, Croatia

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Zagreb, 10 000, Croatia

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Brno, 656 53, Czechia

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Prague, 150 08, Czechia

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Prague, 180 00, Czechia

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Tampere, 33520, Finland

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Heidelberg, Baden-Wurttemberg, 69115, Germany

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Stuttgart, Baden-Wurttemberg, 70190, Germany

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Stuttgart, Baden-Wurttemberg, 70199, Germany

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Augsburg, Bavaria, 86150, Germany

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Coburg, Bavaria, 96450, Germany

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Munich, Bavaria, 80331, Germany

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Fürstenwalde, Brandenburg, 15517, Germany

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Hamburg, Hamburg, 22081, Germany

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Hamburg, Hamburg, 22457, Germany

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Hamburg, Hamburg, 22767, Germany

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Frankfurt am Main, Hesse, 60596, Germany

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Leer, Lower Saxony, 26789, Germany

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Herne, North Rhine-Westphalia, 44623, Germany

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Troisdorf, North Rhine-Westphalia, 53840, Germany

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Velbert, North Rhine-Westphalia, 42551, Germany

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Saarbrücken, Saarland, 66113, Germany

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Halle, Saxony-Anhalt, 06120, Germany

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Magdeburg, Saxony-Anhalt, 39108, Germany

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Kiel, Schleswig-Holstein, 24103, Germany

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Berlin, State of Berlin, 10367, Germany

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Berlin, State of Berlin, 12200, Germany

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Athens, 115 22, Greece

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Athens, 13122, Greece

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Athens, 185 37, Greece

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Neo Faliro, 18547, Greece

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Bari, Apulia, 70126, Italy

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Lecce, Apulia, 73100, Italy

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Ravenna, Emilia-Romagna, 48100, Italy

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Rome, Lazio, 00144, Italy

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Rozzano (MI), Lombardy, 20089, Italy

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Perugia, Umbria, 06156, Italy

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Bialystok, 15-027, Poland

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Olsztyn, 10-226, Poland

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Olsztyn, 10-228, Poland

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Warsaw, 02-781, Poland

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Wroclaw, 53-413, Poland

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Barcelona, 08035, Spain

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Hospitalet de Llobregat (Barcelona), 08907, Spain

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Lleida, 25198, Spain

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Madrid, 28041, Spain

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Santa Cruz de Tenerife, 38320, Spain

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Valencia, 46010, Spain

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Huddersfield, HD3 3EA, United Kingdom

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Ipswich, IP4 5PD, United Kingdom

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London, SE1 9RT, United Kingdom

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Related Publications (2)

• 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.

  PMID: 21406472 BACKGROUND

• 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.

  PMID: 22689807 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2006
• First Posted: May 3, 2006
• Study Start: November 1, 2005
• Primary Completion: June 1, 2007
• Study Completion: October 1, 2010
• Last Updated: February 26, 2016
• Results First Posted: November 30, 2011

Record last verified: 2015-04

Locations

FI (1); IT (6); CZ (3); ES (6); DE (21); CA (3); CR (2); BU (2); PL (5); GB (3); US (87); GR (4); AU (2)