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NCT00820222

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

Completed Phase 3 Results posted Last updated 2 April 2019
What this trial tests

Phase 3 trial testing capecitabine in Metastases, Brain in 540 participants. Completed in 22 March 2018.

Timeline
14 April 2009
Primary endpoint
11 June 2012
22 March 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment540
Start date14 April 2009
Primary completion11 June 2012
Estimated completion22 March 2018
Sites164 locations across Denmark, France, Italy, Russia, Greece, Belgium, Sweden, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Metastases, Brain. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse Primary · From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

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

GroupValue95% CI
Lapatinib Plus Capecitabine8
Trastuzumab Plus Capecitabine12
Progression Free Survival (PFS), as Assessed by the Investigator Secondary · From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

PFS is defined as the interval between the date of randomization and the earliest date of progressive disease (PD), or death due to any cause. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions based on investigator assessment of both CNS and non-CNS for response.

GroupValue95% CI
Lapatinib Plus Capecitabine6.605.72 – 8.11
Trastuzumab Plus Capecitabine8.056.14 – 8.90
Time to First CNS Progression, Defined as the Time From Randomization Until the Date of Documented CNS Progression as the First Site of Relapse Secondary · From randomization until the date of documented CNS progression (average of 10 months). Cut-off 11-Jun-2012

CNS relapse is defined as the appearance of \>=1 enhancing lesion measuring \>=6 mm on T1W 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) with

GroupValue95% CI
Lapatinib Plus Capecitabine8.2± 6.78
Trastuzumab Plus Capecitabine6.7± 6.94
Overall Survival Secondary · From randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012

Overall survival is defined as the time from randomization until death due to any cause or to the date of censor. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contact.

GroupValue95% CI
Lapatinib Plus Capecitabine22.719.5 – NA
Trastuzumab Plus Capecitabine27.323.7 – NA
Number of Participants With Overall Response (OR), as Assessed by the Investigator Secondary · From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

OR is defined as the number of participants with either a confirmed complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD). CR and PR were assessed per Response Evaluation Criteria in Solid Tumors (RECIST). To be assigned a status of PR or CR, a confirmatory disease assessment was to be performed 28 days (4 weeks) or greater after the criteria for response were first met. In addition, a bone scan must have been obtained to rule out the presence of new bone lesion

CR
GroupValue95% CI
Lapatinib Plus Capecitabine8
Trastuzumab Plus Capecitabine12
PR
GroupValue95% CI
Lapatinib Plus Capecitabine65
Trastuzumab Plus Capecitabine73
Overall Response (CR+PR)
GroupValue95% CI
Lapatinib Plus Capecitabine73
Trastuzumab Plus Capecitabine85
Number of Participants With Clinical Benefit (CB) Secondary · From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

CB is defined as the number of participants with evidence of confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) at any time or stable disease (SD, neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD \[defined as at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions\] based on investigator assessment), for at least 24 weeks.

CR
GroupValue95% CI
Lapatinib Plus Capecitabine8
Trastuzumab Plus Capecitabine12
PR
GroupValue95% CI
Lapatinib Plus Capecitabine65
Trastuzumab Plus Capecitabine73
SD >= 24 weeks
GroupValue95% CI
Lapatinib Plus Capecitabine39
Trastuzumab Plus Capecitabine33
Clinical Benefit (CR + PR + SD >= 24 weeks)
GroupValue95% CI
Lapatinib Plus Capecitabine112
Trastuzumab Plus Capecitabine118
Duration of Response Secondary · From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 10 months). Cut-off 11-Jun-2012

Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) until the first documented sign of PD (at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions) or death due to breast cancer. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contac

GroupValue95% CI
Lapatinib Plus Capecitabine6.25.3 – 10.6
Trastuzumab Plus Capecitabine8.46.0 – 21.6
Number of Participants With CNS Progression at Any Time Secondary · From the time of randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012

CNS progression was documented by a brain scan and was indicated by the investigator on the follow-up electronic Case Report Form. CNS relapse is defined as the appearance of \>=1 enhancing lesion measuring \>=6 mm on T1W 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, with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without sympto

GroupValue95% CI
Lapatinib Plus Capecitabine17
Trastuzumab Plus Capecitabine15
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Secondary · From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months).

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was related to study drug. AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE.

Palmar-plantar erythrodysaesthesia syndrome
GroupValue95% CI
Lapatinib Plus Capecitabine29
Trastuzumab Plus Capecitabine45
Diarrhoea
GroupValue95% CI
Lapatinib Plus Capecitabine19
Trastuzumab Plus Capecitabine22
Aspartate aminotransferase increased
GroupValue95% CI
Lapatinib Plus Capecitabine11
Trastuzumab Plus Capecitabine4
Neutropenia
GroupValue95% CI
Lapatinib Plus Capecitabine9
Trastuzumab Plus Capecitabine18
Asthenia
GroupValue95% CI
Lapatinib Plus Capecitabine9
Trastuzumab Plus Capecitabine6
Fatigue
GroupValue95% CI
Lapatinib Plus Capecitabine7
Trastuzumab Plus Capecitabine4
Alanine aminotransferase increased
GroupValue95% CI
Lapatinib Plus Capecitabine4
Trastuzumab Plus Capecitabine6
Hypokalaemia
GroupValue95% CI
Lapatinib Plus Capecitabine3
Trastuzumab Plus Capecitabine11

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lapatinib Plus Capecitabine
Serious: 41/270 (15%)
Deaths: 12/270
Trastuzumab Plus Capecitabine
Serious: 51/267 (19%)
Deaths: 3/267

Serious adverse events (93 terms)

ReactionSystemLapatinib Plus CapecitabineTrastuzumab Plus Capecitab…
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Ejection fraction decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Left ventricular dysfunctionCardiac disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Non-cardiac chest painGeneral disorders
PneumoniaInfections and infestations
Septic shockInfections and infestations
Urinary tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
HyperuricaemiaMetabolism and nutrition disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Deep vein thrombosisVascular disorders
ThrombophlebitisVascular disorders
ThrombosisVascular disorders
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Other adverse events (28 terms — click to expand)

ReactionSystemLapatinib Plus CapecitabineTrastuzumab Plus Capecitab…
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
HyperbilirubinaemiaHepatobiliary disorders
Alanine aminotransferase increasedInvestigations
FatigueGeneral disorders
Aspartate aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
Mucosal inflammationGeneral disorders
PyrexiaGeneral disorders
StomatitisGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Nail disorderSkin and subcutaneous tissue disorders
Blood bilirubin increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Blood alkaline phosphatase increasedInvestigations
HeadacheNervous system disorders
Back painMusculoskeletal and connective tissue disorders
Dry skinSkin and subcutaneous tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Diarrhoea, Neutropenia, Pulmonary embolism, Pyrexia, Ejection fraction decreased, Hypokalaemia, Left ventricular dysfunction, Constipation.

Data from ClinicalTrials.gov NCT00820222 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Treatment of Brain Metastases.
    Lin X, DeAngelis LM. · · 2015 · cited 295× · PMID 26282648 · DOI 10.1200/jco.2015.60.9503
  2. Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer.
    Xuhong JC, Qi XW, Zhang Y, Jiang J. · · 2019 · cited 118× · PMID 31720077
  3. Emerging strategies for treating brain metastases from breast cancer.
    Kodack DP, Askoxylakis V, Ferraro GB, Fukumura D, et al · · 2015 · cited 116× · PMID 25670078 · DOI 10.1016/j.ccell.2015.01.001
  4. Breast Cancer Brain Metastasis-Overview of Disease State, Treatment Options and Future Perspectives.
    Watase C, Shiino S, Shimoi T, Noguchi E, et al · · 2021 · cited 68× · PMID 33802424 · DOI 10.3390/cancers13051078
  5. EGFR and HER2 signaling in breast cancer brain metastasis.
    Sirkisoon SR, Carpenter RL, Rimkus T, Miller L, et al · · 2016 · cited 65× · PMID 26709660 · DOI 10.2741/e765
  6. Unsanctifying the sanctuary: challenges and opportunities with brain metastases.
    Puhalla S, Elmquist W, Freyer D, Kleinberg L, et al · · 2015 · cited 46× · PMID 25846288 · DOI 10.1093/neuonc/nov023
  7. Characteristics and follow-up of postmarketing studies of conditionally authorized medicines in the EU.
    Hoekman J, Klamer TT, Mantel-Teeuwisse AK, Leufkens HG, et al · · 2016 · cited 42× · PMID 26992001 · DOI 10.1111/bcp.12940
  8. Landscape of combination therapy trials in breast cancer brain metastasis.
    Fares J, Kanojia D, Rashidi A, Ulasov I, et al · · 2020 · cited 33× · PMID 32086955 · DOI 10.1002/ijc.32937

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00820222.

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