Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in ErbB2 (HER2) Positive Metastatic Breast Cancer

NCT ID: NCT00820222

Last Updated: 2019-04-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

540 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-14

Study Completion Date

2018-03-22

Brief Summary

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This open label study was designed to evaluate Lapatinib effect on incidence of brain metastases in ErbB2 (HER2) positive metastatic breast cancer patients exposed to prior taxanes or anthracyclines.

Detailed Description

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The study was terminated based on the IDMC recommendation in 2012, collection of efficacy outcome measures was discontinued and all primary and secondary outcome measures were reported in 2012.

An amendment protocol allowed subjects who were on study treatment to enroll in a Long Term Follow Up (LTFU) phase if they had evidence of clinical benefit but no local access to standard of care treatments. Subjects received study treatment until disease progression, unacceptable toxicity, or subject withdrawal. In LTFU only Adverse Events data were collected. For the LTFU the Outcome Measure "Number of participants with the indicated Grade 3 or Grade 4 Adverse Events (AEs) occurring in \>=2% of participants in either treatment arm" and "Adverse Events" were updated.

Conditions

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Metastases, Brain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Lapatinib plus capecitabine

Lapatinib 1250 mg once daily and capecitabine 2000mg/m2/day, days 1-14, every 21 days

Group Type EXPERIMENTAL

capecitabine

Intervention Type DRUG

oral medication; daily dose divided into morning and evening dose and taken for 14 days of 21 day cycle

lapatinib

Intervention Type DRUG

oral medication; daily dose taken once a day

Trastuzumab plus capecitabine

trastuzumab loading dose of 8mg/kg followed by 6mg/kg q3weekly infusions, and capecitabine 2500mg/m2/day, days 1-14, every 21 days

Group Type ACTIVE_COMPARATOR

capecitabine

Intervention Type DRUG

oral medication; daily dose divided into morning and evening dose and taken for 14 days of 21 day cycle

trastuzumab

Intervention Type DRUG

infusion therapy; loading dose of 8mg/kg, followed by 6mg/kg given every 3 weeks

Interventions

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capecitabine

oral medication; daily dose divided into morning and evening dose and taken for 14 days of 21 day cycle

Intervention Type DRUG

lapatinib

oral medication; daily dose taken once a day

Intervention Type DRUG

trastuzumab

infusion therapy; loading dose of 8mg/kg, followed by 6mg/kg given every 3 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Females at least 18 years old;
* ECOG Performance Status 0-2;
* Histologically or cytologically confirmed HER2-positive invasive breast cancer, with Stage IV disease;
* Prior treatment with taxanes or anthracyclines is required;
* Prior treatment with other chemotherapeutic agents, trastuzumab, endocrine and radiation therapy is permitted;
* Baseline LVEF ≥ 50% and not lower than the institutional lower limit of normal;
* Concurrent treatment with bisphosphonates is permitted, however treatment must be initiated prior to the first dose of study therapy;
* Able to swallow and retain oral medications;
* Women with potential to have children must be willing to practice acceptable methods of birth control during the study;
* Normal organ and marrow function.

Exclusion Criteria

* History and/or current evidence of CNS metastases. Baseline MRI scan by Independent Reviewer to confirm no brain mets;
* Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
* Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab (including but not limited to trastuzumab-DM1 and neratinib) and capecitabine;
* Known DPD deficiency;
* Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for treatment of cancer;
* History of allergic reactions attributed to compounds chemically related to lapatinib (quinazolines), capecitabine, fluorouracil or any excipients;
* Concomitant use of CYP3A4 inhibitors or inducers;
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel;
* History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast and other known contraindication to MRI;
* Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the patient's safety or compliance to study procedures;
* have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease);
* Any on-going toxicity from prior anti cancer therapy except alopecia;
* Active cardiac disease;
* Uncontrolled infection;
* History of other malignancy, unless curatively treated with no evidence of disease for at least 5 years, subjects with adequately treated DCIS or LCIS, adequately treated non-melanoma skin cancer or curatively treated in-situ cancer of the cervix are eligible;
* Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of protocol treatment;
* Pregnant or lactating females.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Goodyear, Arizona, United States

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Tucson, Arizona, United States

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Jonesboro, Arkansas, United States

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Anaheim, California, United States

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Greenbrae, California, United States

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Sacramento, California, United States

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Santa Barbara, California, United States

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Washington D.C., District of Columbia, United States

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Boca Raton, Florida, United States

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Coral Springs, Florida, United States

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Hollywood, Florida, United States

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Warrenville, Illinois, United States

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Metairie, Louisiana, United States

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St Louis, Missouri, United States

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Great Falls, Montana, United States

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Voorhees Township, New Jersey, United States

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Durham, North Carolina, United States

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Antwerp, , Belgium

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Brussels, , Belgium

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Sint-Niklaas, , Belgium

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Aarhus, , Denmark

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Angers, , France

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Avignon, , France

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Bayonne, , France

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Besançon, , France

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Caen, , France

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Colmar, , France

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Dechy, , France

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Nancy, , France

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Paris, , France

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Reims, , France

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Reims, , France

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Saint-Grégoire, , France

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Saint-Priest-en-Jarez, , France

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Strasbourg, , France

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Vannes, , France

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Ravensburg, Baden-Wurttemberg, Germany

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Eggenfelden, Bavaria, Germany

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Fürth, Bavaria, Germany

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Landshut, Bavaria, Germany

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Munich, Bavaria, Germany

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Munich, Bavaria, Germany

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Nuremberg, Bavaria, Germany

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Rosenheim, Bavaria, Germany

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Würzburg, Bavaria, Germany

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Potsdam, Brandenburg, Germany

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Frankfurt am Main, Hesse, Germany

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Wiesbaden, Hesse, Germany

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Bottrop, North Rhine-Westphalia, Germany

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Cologne, North Rhine-Westphalia, Germany

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Cologne, North Rhine-Westphalia, Germany

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Duisburg, North Rhine-Westphalia, Germany

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Goch, North Rhine-Westphalia, Germany

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Herne, North Rhine-Westphalia, Germany

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Velbert, North Rhine-Westphalia, Germany

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Witten, North Rhine-Westphalia, Germany

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Würselen, North Rhine-Westphalia, Germany

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Mainz, Rhineland-Palatinate, Germany

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Speyer, Rhineland-Palatinate, Germany

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Halle, Saxony-Anhalt, Germany

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Lübeck, Schleswig-Holstein, Germany

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Berlin, , Germany

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Tatabánya, , Hungary

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Veszprém, , Hungary

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Bologna, Emilia-Romagna, Italy

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Bologna, Emilia-Romagna, Italy

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Meldola (FC), Emilia-Romagna, Italy

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Rimini, Emilia-Romagna, Italy

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Udine, Friuli Venezia Giulia, Italy

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Rome, Lazio, Italy

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Monza, Lombardy, Italy

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Treviglio (BG), Lombardy, Italy

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Novara, Piedmont, Italy

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Fermo (AP), The Marches, Italy

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Trento, Trentino-Alto Adige, Italy

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Lido Di Camaiore (LU), Tuscany, Italy

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Pisa, Tuscany, Italy

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Perugia, Umbria, Italy

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Varese, , Italy

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Bydgoszcz, , Poland

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Bytom, , Poland

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Gliwice, , Poland

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Konin, , Poland

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Kirov, , Russia

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Nizhny Novgorod, , Russia

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Petrozavodsk, , Russia

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Veliky Novgorod, , Russia

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Voronezh, , Russia

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Vsevolozhsk, , Russia

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A Coruña, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Cáceres, , Spain

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Hospitalet de Llobregat (Barcelona), , Spain

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Jerez (Cadiz), , Spain

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Lleida, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Palma de Mallorca, , Spain

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Palma de Mallorca, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Seville, , Spain

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Torrevieja (Alicante), , Spain

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Valencia, , Spain

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Stockholm, , Sweden

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Uppsala, , Sweden

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Vaxjo, , Sweden

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Västerås, , Sweden

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Songkhla, , Thailand

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Edinburgh, Midlothian, United Kingdom

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Birmingham, West Midlands, United Kingdom

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Aberdeen, , United Kingdom

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Burton-on-Trent, , United Kingdom

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Cottingham, Hull, , United Kingdom

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Huddersfield, , United Kingdom

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Ipswich, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Maidstone, , United Kingdom

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Nottingham, , United Kingdom

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Peterborough, , United Kingdom

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Sheffield, , United Kingdom

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Shrewsbury, , United Kingdom

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Southampton, , United Kingdom

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Wolverhampton, , United Kingdom

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Worthing, , United Kingdom

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Countries

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United States Belgium Denmark France Germany Greece Hungary Italy Poland Russia Spain Sweden Thailand United Kingdom

References

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Pivot X, Manikhas A, Zurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. doi: 10.1200/JCO.2014.57.1794. Epub 2015 Jan 20.

Reference Type DERIVED
PMID: 25605838 (View on PubMed)

Other Identifiers

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111438

Identifier Type: -

Identifier Source: org_study_id

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