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NCT00470704

Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer

Completed Phase 2 Results posted Last updated 19 December 2024
What this trial tests

Phase 2 trial testing Lapatinib in Breast Cancer in 87 participants. Completed in 20 August 2024.

Timeline
14 May 2007
Primary endpoint
30 November 2013
20 August 2024

Quick facts

Lead sponsorNancy Lin, MD
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment87
Start date14 May 2007
Primary completion30 November 2013
Estimated completion20 August 2024
Sites9 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Nancy Lin, MD — full company profile →

Who can join

18 and older, any sex, with Breast Cancer. 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.

Objective Response Rate Primary · 8 weeks

The objective response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as refere

GroupValue95% CI
Cohort 150.033.8 – 66.2
Cohort 222.211.3 – 37.3
Top 3 Most Common Treatment RelatedToxicities Secondary · Up to 93 months

Assessed by -Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Top 3 treatment-related all-grade adverse events in terms of incidence. Treatment Related is discerned as follows: Yes: There is a plausible temporal relationship between the onset of the AE and administration of atezolizumab or bevacizumab, and the AE cannot be readily explained by the patient's clinical state, intercurrent illness, or concomitant therapies; and/or the AE follows a known pattern of response to atezolizumab or bevacizumab or with similar treatments; and/or the AE resolves upon discontinuation of

Diarrhea
GroupValue95% CI
Cohort 127
Cohort 228
Fatigue
GroupValue95% CI
Cohort 121
Cohort 224
Acne
GroupValue95% CI
Cohort 120
Cohort 215
Sites of First Progression Secondary · Up to 93 months

Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST) as follows: \- \>20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including baseline if it's the smallest). The sum must also demonstrate an increase of \>5 mm. OR -Appearance of new lesions and/or unequivocal progression of non-target lesions. It must be representative of overall disease status change, not a single lesion increase. For patients with PD at the first on-treatment imaging assessment, patients will be allowed to remain on study

Central Nervous System (CNS)
GroupValue95% CI
Cohort 13
Cohort 23
Non-CNS
GroupValue95% CI
Cohort 131
Cohort 239
CNS and Non-CNS
GroupValue95% CI
Cohort 13
Cohort 20
NA
GroupValue95% CI
Cohort 14
Cohort 24
Clinical Benefit Rate Secondary · Up to 93 months

Clinical Benefit Rate is the percentage of participants who achieve clinical benefit from the study treatment. Clinical benefit is defined as at least 24 weeks of confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD). SD or better is achieved if the following are true: Target Lesions: -At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of a

GroupValue95% CI
Cohort 157.540.9 – 73
Cohort 240.025.7 – 55.7
3-Year Overall Survival Secondary · Up to 93 months

Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. 3-Year survival is calculated using Kaplan-Meier methods.

GroupValue95% CI
Cohort 1.62.47 – .81
Cohort 2.39.26 – .57
Median Time to Progression Secondary · Up to 93 months

Time to progression (TTP) is defined as the time from study entry to disease progression by RECIST. Subjects are considered to have progressed if they discontinue treatment due to clinical deterioration from breast cancer or die on-treatment of any cause. TTP is censored at the time of initiation of alternative therapy or time of last contact. The time to progression is calculated using a Kaplan-Meier emthods. Progression is defined by RECIST as: \>20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including baseline if it's the smalles

GroupValue95% CI
Cohort 17.43.9 – 9.3
Cohort 25.33.7 – 6.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 93 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1
Serious: 2/41 (5%)
Deaths: 15/41
Cohort 2
Serious: 7/46 (15%)
Deaths: 34/46

Serious adverse events (5 terms)

ReactionSystemCohort 1Cohort 2
Diarrhea w/o prior colostomyGastrointestinal disorders
FatigueGeneral disorders
Diarrhea w/o prior colostomyGastrointestinal disorders
HypokalemiaMetabolism and nutrition disorders
GI-otherGastrointestinal disorders
Other adverse events (155 terms — click to expand)

ReactionSystemCohort 1Cohort 2
Diarrhea w/o prior colostomyGastrointestinal disorders
FatigueGeneral disorders
Rash: acne/acneiformSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
AST, SGOTInvestigations
HyperglycemiaMetabolism and nutrition disorders
HemoglobinBlood and lymphatic system disorders
Head/headacheNervous system disorders
ALT, SGPTInvestigations
HypertensionVascular disorders
Alkaline phosphataseInvestigations
Back, painMusculoskeletal and connective tissue disorders
Nail changesSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
DizzinessNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Neuropathy-sensoryNervous system disorders
Rash/desquamationSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
Hot flashesVascular disorders
Muco/stomatitis by exam, oral cavityGastrointestinal disorders
Pruritus/itchingSkin and subcutaneous tissue disorders
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
Chest wall, painMusculoskeletal and connective tissue disorders
DyspepsiaGastrointestinal disorders
Edema limbGeneral disorders
Hand-foot reactionSkin and subcutaneous tissue disorders
Nose, hemorrhageRespiratory, thoracic and mediastinal disorders
Skin-otherSkin and subcutaneous tissue disorders
Abdomen, painGastrointestinal disorders
ArthritisMusculoskeletal and connective tissue disorders
BicarbonateMetabolism and nutrition disorders
Dry skinSkin and subcutaneous tissue disorders
Fever w/o neutropeniaGeneral disorders
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders

Most-reported serious reactions: Diarrhea w/o prior colostomy, Fatigue, Diarrhea w/o prior colostomy, Hypokalemia, GI-other.

Data from ClinicalTrials.gov NCT00470704 adverse events section.

Sponsor's own description

In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Finally, we are studying genes and proteins in the tumor tissue that may lead to sensitivity or resistance to Herceptin, and to the combination of Herceptin plus lapatinib. Lapatinib is a compound that may stop cancer cells from growing. Other research studies suggest that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer.

Publications & conference data

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

  1. Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003).
    Lin NU, Guo H, Yap JT, Mayer IA, et al · · 2015 · cited 46× · PMID 26169615 · DOI 10.1200/jco.2014.60.0353
  2. 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
  3. Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.
    Hurvitz SA, Kakkar R. · · 2012 · cited 18× · PMID 24367193 · DOI 10.2147/bctt.s29996
  4. Treating Advanced Unresectable or Metastatic HER2-Positive Breast Cancer: A Spotlight on Tucatinib.
    Ulrich L, Okines AFC. · · 2021 · cited 13× · PMID 34079368 · DOI 10.2147/bctt.s268451
  5. Novel combinations for the treatment of metastatic breast cancer.
    Vahdat LT. · · 2010 · cited 2× · PMID 24281029 · DOI 10.3390/cancers2010001
  6. Detection of heterogeneous resistance mechanisms to tyrosine kinase inhibitors from cell-free DNA.
    Parsons HA, Messer C, Santos K, Weiss J, et al · · 2025 · PMID 40930104 · DOI 10.1016/j.xgen.2025.100987

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