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

NCT00820222 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 111438
• Study Type: interventional
• Target: 540
• Locations: 14 countries
• Sites: 164

Brief Summary

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.

Conditions

Metastases, Brain

Keywords

ErbB2; HERCEPTIN; XELODA; ErbB1; TYKERB; metastatic breast cancer; trastuzumab; breast cancer; capecitabine; lapatinib; brain metastases; HER2 positive; TYVERB

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse

  CNS relapse is defined as the appearance of \>=1 enhancing lesion measuring \>=6 millimeters (mm) on T1Weighted (T1W) Magnetic Resonance Imaging (MRI) without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a \<6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.

  From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

Secondary Outcomes (10)

• Progression Free Survival (PFS), as Assessed by the Investigator

  From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

• Time to First CNS Progression, Defined as the Time From Randomization Until the Date of Documented CNS Progression as the First Site of Relapse

  From randomization until the date of documented CNS progression (average of 10 months). Cut-off 11-Jun-2012

• Overall Survival

  From randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012

• Number of Participants With Overall Response (OR), as Assessed by the Investigator

  From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

• Number of Participants With Clinical Benefit (CB)

  From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

Study Arms (2)

Lapatinib plus capecitabine

EXPERIMENTAL

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

Drug: capecitabine; Drug: lapatinib

Trastuzumab plus capecitabine

ACTIVE COMPARATOR

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

Drug: capecitabine; Drug: trastuzumab

Interventions

capecitabine DRUG

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

Lapatinib plus capecitabine; Trastuzumab plus capecitabine

lapatinib DRUG

oral medication; daily dose taken once a day

Lapatinib plus capecitabine

trastuzumab DRUG

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

Trastuzumab plus capecitabine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (164)

Novartis Investigative Site

Goodyear, Arizona, 85338, United States

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Tucson, Arizona, 85715, United States

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Jonesboro, Arkansas, 72401, United States

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Anaheim, California, 92801, United States

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Greenbrae, California, 94904-2007, United States

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Sacramento, California, 95816, United States

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Santa Barbara, California, 93105, United States

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Washington D.C., District of Columbia, 20007, United States

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Boca Raton, Florida, 33486, United States

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Coral Springs, Florida, 33065, United States

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Hollywood, Florida, 33021, United States

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Warrenville, Illinois, 60555, United States

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Metairie, Louisiana, 70006, United States

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St Louis, Missouri, 63110, United States

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Great Falls, Montana, 59405, United States

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Voorhees Township, New Jersey, 08043, United States

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Durham, North Carolina, 27710, United States

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Antwerp, 2020, Belgium

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Brussels, 1180, Belgium

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Sint-Niklaas, 9100, Belgium

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Aarhus, 8000 Aarhus C, Denmark

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Angers, 49933, France

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Avignon, 84000, France

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Bayonne, 64109, France

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Besançon, 25030, France

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Caen, 14076, France

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Colmar, 68000, France

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Dechy, 59187, France

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Nancy, 54100, France

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Paris, 75651, France

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Reims, 51056, France

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Reims, 51100, France

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Saint-Grégoire, 35760, France

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Saint-Priest-en-Jarez, 42271, France

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Strasbourg, 67000, France

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Vannes, 56000, France

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Ravensburg, Baden-Wurttemberg, 88212, Germany

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Eggenfelden, Bavaria, 84307, Germany

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Fürth, Bavaria, 90766, Germany

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Landshut, Bavaria, 84028, Germany

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Munich, Bavaria, 81675, Germany

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Munich, Bavaria, 81925, Germany

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Nuremberg, Bavaria, 90449, Germany

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Rosenheim, Bavaria, 83022, Germany

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Würzburg, Bavaria, 97070, Germany

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Potsdam, Brandenburg, 14467, Germany

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Frankfurt am Main, Hesse, 60389, Germany

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Wiesbaden, Hesse, 65199, Germany

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Bottrop, North Rhine-Westphalia, 46236, Germany

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Cologne, North Rhine-Westphalia, 50935, Germany

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Cologne, North Rhine-Westphalia, 51067, Germany

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Duisburg, North Rhine-Westphalia, 47166, Germany

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Goch, North Rhine-Westphalia, 47574, Germany

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Herne, North Rhine-Westphalia, 44623, Germany

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Velbert, North Rhine-Westphalia, 42551, Germany

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Witten, North Rhine-Westphalia, 58452, Germany

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Würselen, North Rhine-Westphalia, 52146, Germany

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Mainz, Rhineland-Palatinate, 55131, Germany

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Speyer, Rhineland-Palatinate, 67346, Germany

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Halle, Saxony-Anhalt, 06120, Germany

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Lübeck, Schleswig-Holstein, 23562, Germany

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Berlin, 14169, Germany

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Brandenburg, 14770, Germany

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Bremen, 28209, Germany

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Hamburg, 20095, Germany

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Hamburg, 22081, Germany

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Athens, 115 26, Greece

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Athens, 115 28, Greece

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N. Kifisia, Athens, 145 64, Greece

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Neo Faliro, 18547, Greece

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Pátrai, 26504, Greece

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Peiraius, 185 37, Greece

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Thessaloniki, Greece

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Budapest, 1082, Hungary

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Budapest, 1122, Hungary

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Budapest, 1125, Hungary

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Kaposvár, 7400, Hungary

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Tatabánya, 2800, Hungary

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Veszprém, 8200, Hungary

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Bologna, Emilia-Romagna, 40138, Italy

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Bologna, Emilia-Romagna, 40139, Italy

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Meldola (FC), Emilia-Romagna, 47014, Italy

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Rimini, Emilia-Romagna, 47900, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Rome, Lazio, 00144, Italy

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Monza, Lombardy, 20052, Italy

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Treviglio (BG), Lombardy, 24047, Italy

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Novara, Piedmont, 28100, Italy

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Fermo (AP), The Marches, 63023, Italy

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Trento, Trentino-Alto Adige, 38100, Italy

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Lido Di Camaiore (LU), Tuscany, 55043, Italy

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Pisa, Tuscany, 56126, Italy

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Perugia, Umbria, 06132, Italy

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Varese, 21100, Italy

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Bydgoszcz, 85-796, Poland

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Bytom, 41-902, Poland

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Gliwice, 44-101, Poland

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Konin, 62-500, Poland

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Lodz, 93-509, Poland

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Olsztyn, 10-228, Poland

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Rzeszów, 35-021, Poland

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Wroclaw, 51-124, Poland

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Wroclaw, 53-413, Poland

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Arkhangelsk, 163045, Russia

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Chelyabinsk, 454087, Russia

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Kazan', 420029, Russia

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Kirov, 610021, Russia

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Moscow, 115 478, Russia

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Moscow, 117997, Russia

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Moscow Region, 143 423, Russia

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Nizhny Novgorod, 603081, Russia

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Obninsk, 249036, Russia

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Petrozavodsk, 185035, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197758, Russia

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Tver', 170008, Russia

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Veliky Novgorod, 173016, Russia

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Voronezh, 394062, Russia

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Vsevolozhsk, 188663, Russia

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A Coruña, 15009, Spain

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Barcelona, 08003, Spain

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Barcelona, 08035, Spain

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Cáceres, 10003, Spain

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Hospitalet de Llobregat (Barcelona), 08907, Spain

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Jerez (Cadiz), 11047, Spain

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Lleida, 25198, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Málaga, 29010, Spain

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Palma de Mallorca, 07010, Spain

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Palma de Mallorca, 07198, Spain

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Santiago de Compostela, 15706, Spain

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Seville, 41013, Spain

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Seville, 41014, Spain

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Torrevieja (Alicante), 03186, Spain

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Valencia, 46010, Spain

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Stockholm, SE-171 76, Sweden

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Uppsala, SE-751 85, Sweden

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Vaxjo, SE-351 85, Sweden

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Västerås, SE-721 89, Sweden

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Chiang Mai, 50200, Thailand

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Songkhla, 90110, Thailand

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Edinburgh, Midlothian, EH4 2XU, United Kingdom

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Birmingham, West Midlands, B18 7QH, United Kingdom

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Aberdeen, AB25 2ZN, United Kingdom

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Burton-on-Trent, DE13 0RB, United Kingdom

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Cottingham, Hull, HU16 5JQ, United Kingdom

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Huddersfield, HD3 3EA, United Kingdom

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Ipswich, IP4 5PD, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, NW3 2QG, United Kingdom

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London, SW17 0QT, United Kingdom

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Maidstone, ME16 9QQ, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Peterborough, PE3 9GZ, United Kingdom

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Sheffield, S10 2SJ, United Kingdom

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Shrewsbury, SY3 8XQ, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Wolverhampton, WV10 0QP, United Kingdom

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Worthing, BN11 2DH, United Kingdom

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Related Publications (1)

• 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.

  PMID: 25605838 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Breast Neoplasms

Interventions

Capecitabine; Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

In 2012 enrollment was stopped and collection of efficacy outcome measures discontinued. Subjects were allowed to enroll in a Long Term Follow Up to provide continued access in which only AE information was collected.

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  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: January 8, 2009
• First Posted: January 12, 2009
• Study Start: April 14, 2009
• Primary Completion: June 11, 2012
• Study Completion: March 22, 2018
• Last Updated: April 2, 2019
• Results First Posted: March 15, 2013

Record last verified: 2019-03

Locations

DK (1); ES (18); US (17); BE (3); SE (4); GB (18); TH (4); RU (17); FR (15); DE (30); IT (15); HU (6); PL (9); GR (7)