A Phase 2 interventional study of Trastuzumab and Paclitaxel in Neoplasms, Breast, sponsored by GlaxoSmithKline. Completed at 23 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-11-11.
Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment
This study will examine safety and efficacy of Lapatinib in combination with a standard neoadjuvant chemotherapy including 5FU, Epirubicin, Cyclophosphamide and Paclitaxel. Tumor tissue will be obtained at 3 timepoints (optional 4th) to evaluate tumor response to treatment.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 100 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
Counted across the registry records on this site, refreshed daily.
Table 1 Baseline Laboratory Values
Hematologic:
ANC (absolute neutrophil count) >1.5 x 109/L hemoglobin >9 g/dL platelets >75 x 109/L
Hepatic:
albumin >2.5 g/dL serum bilirubin \<1.25 x ULN AST / ALT \<3 x ULN if no documented liver metastases AST / ALT \<3 x ULN with documented liver metastases
Renal:
serum creatinine \<2.0 mg/dL
Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal)
Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following:
Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or Consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only) where not contraindicated for this subject population or per local practice.; or barrier methods, including diaphragm or condom with a spermicide.
Please note that breast cancer subjects on this trial cannot receive injectable levonorgestrel or injectable progestogen due to the potential for an adverse effect of anti-hormonal therapies on chemotherapy administered for breast cancer [Albain, 2002]. Progestogen may also affect the proliferative rate of endocrine-responsive tumors.
Exclusion Criteria:
History of uncontrolled or symptomatic angina History of arrhythmias requiring medications, or clinically significant Myocardial infarction \<6 months from study entry Uncontrolled or symptomatic congestive heart failure Ejection fraction below the institutional normal limit Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
Trastuzumab alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles and Paclitaxel for 4 (21 day) cycles then continued trastuzumab until time of definitive surgery
Drug: Trastuzumab · Drug: Paclitaxel · Drug: FEC75
Lapatinib alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued lapatinib until time of definitive surgery
Drug: Paclitaxel · Drug: FEC75 · Drug: Lapatinib
Trastuzumab + Lapatinib for 2 weeks then added FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued trastuzumab + lapatinib until time of definitive surgery
Drug: Trastuzumab · Drug: Paclitaxel · Drug: FEC75 · Drug: Lapatinib
4mg/kg IV loading dose followed by 2mg/kg IV weekly
80mg/m2 IV weekly for 4 (21 day) cycles
5FU 500mg/m2 + Epirubicin 75 mg/m2 + cyclophosphamide 500 mg/m2 IV on day 1 of 4 (21 day) cycles
1250 mg oral daily dose in arm 2, 750 mg oral daily dose for FEC cycles and then 1000 mg oral daily dose during the Paclitaxel cycles in arm 3
Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy
A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ \[DCIS\] or lobular carcinoma in situ \[LCIS\] was allowed). A pCR in the axillary lymph node(s) was defined as no evidence of breast cancer cells in the lymph node (including subcapsular sinus). Overall pCR was defined as the sum of pCR in the breast and pCR in the lymph nodes. 26 weeks of therapy comprised the 2-week run-in phase, 12 weeks of treatment with FEC, and 12 weeks of treatment with Paclitaxel.
Time frame: Week 26
Percentage of Participants With Clinical Complete Response (cCR) at 26 Weeks or at End of Treatment (EOT) or Early Withdrawal
cCR was defined as the percentage of participants achieving either a Complete Response (CR) or a Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Time frame: Week 26 or EOT or Early withdrawal
Percentage of Participants (Par.) With Disease-free Survival (DFS) at the End of 5 Years From Randomization
Percentage is the Kaplan Meier estimate of DFS. DFS is time from randomization until disease recurrence (contralateral breast cancer; second primary cancer; progression during neo-adjuvant treatment; or death from any cause). Par. who experienced progression during treatment and were withdrawn were considered to have a DFS event at withdrawal.
Time frame: From first dose date until disease progression, assessed up to a maximum of 5 years
Number of Participants With the Indicated Electrocardiogram (ECG) Status at Baseline and at EOT or Early Withdrawal
12-lead ECGs were performed, and participants were classified as having normal ECG, abnormal- not clinically significant (NCS) ECG, and abnormal-clinically significant (CS) ECG per investigator opinion and reported result.
Time frame: Baseline and EOT (up to Week 26) or Early withdrawal
Cumulative Number of Participants With at Least One Decrease of More Than or Equal to 20% in Left Ventricular Ejection Fraction (LVEF) at the Indicated Time Points Compared to LVEF at Baseline
LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function. LVEF was measured by performing echocardiogram (ECHO). If ECHO could not be performed or if the investigator believed that it was not conclusive to evaluate LVEF, then a multigated acquisition (MUGA) scan was performed.
Time frame: Weeks 3, 9, and 15; EOT or early withdrawal; and 3- and 6-month survival follow-up after last chemotherapy course
Mean Intra-tumoral Expression of the Indicated Proteins at Baseline and Day 14
Expression (exp) of biomarker proteins (prot) were analyzed to determine if individual prot levels either in the Baseline or Day 14 breast tumor biopsy specimen correlated with breast pCR. A biomarker indicates a change in exp or state of a prot that correlates with the risk or disease progression, or with the susceptibility of the disease to a given treatment. Biomarkers are characteristic biological properties that can be detected and measured in parts of the body like blood or tissue. pCR=yes: participants (par.) had breast pCR. pCR=no: par. did not have breast pCR. Prot exp values are represented as normalized, scaled values; the unit of measurement is unit-less. Raw exp values were processed as follows: background subtraction of the raw exp value, then that value divided by beta-acting exp to normalize the exp value. A Standard Z score was calculated to scale the exp value.
Time frame: Tumor core biopsy taken at Baseline and Treatment Day 14
Cancer Stem Cells and the Correlation to Response/Non-response to Treatment
Stem cell data were of poor quality and thus could not be analyzed. Increases or decreases in cancer stem cells and how the changes correlated with response/non-response to treatment were to have been assessed.
Time frame: Tumor core biopsy taken at Baseline and Treatment Day 14
Transcriptional Profiling of Total RNA and the Correlation to Response/Non-response to Treatment
Transcriptional data were of poor quality and thus could not be analyzed. Gene pathways that correlate with response/non-response to treatment were to have been evaluated. The unit of measure is unit less; however, the processed values would be considered normalized relative expression level.
Time frame: Tumor core biopsy taken at Baseline and Treatment Day 14
| Milestone | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| Started | 33 | 34 | 33 |
| Completed | 21 | 24 | 15 |
| Not completed | 12 | 10 | 18 |
| Withdrew: Lost to follow-up | 6 | 0 | 3 |
| Withdrew: Protocol violation | 0 | 1 | 1 |
| Withdrew: Withdrawal by subject | 3 | 0 | 4 |
| Withdrew: Death | 0 | 2 | 3 |
| Withdrew: Adverse event | 1 | 2 | 3 |
| Withdrew: Did not complete study dosing | 1 | 0 | 0 |
| Withdrew: Worsening peripheral neuropathy | 1 | 0 | 0 |
| Withdrew: Disease progression | 0 | 4 | 1 |
| Withdrew: Disease recurrence | 0 | 1 | 0 |
| Withdrew: Sponsor request | 0 | 0 | 1 |
| Withdrew: Physician decision | 0 | 0 | 1 |
| Withdrew: Completed 5 years | 0 | 0 | 1 |
A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ \[DCIS\] or lobular carcinoma in situ \[LCIS\] was allowed). A pCR in the axillary lymph node(s) was defined as no evidence of breast cancer cells in the lymph node (including subcapsular sinus). Overall pCR was defined as the sum of pCR in the breast and pCR in the lymph nodes. 26 weeks of therapy comprised the 2-week run-in phase, 12 weeks of treatment with FEC, and 12 weeks of treatment with Paclitaxel.
| percentage of participants | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy | 54.0 | 45.0 | 74.0 |
cCR was defined as the percentage of participants achieving either a Complete Response (CR) or a Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
| percentage of participants | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| Percentage of Participants With Clinical Complete Response (cCR) at 26 Weeks or at End of Treatment (EOT) or Early Withdrawal | 61.0 | 68.0 | 61.0 |
Percentage is the Kaplan Meier estimate of DFS. DFS is time from randomization until disease recurrence (contralateral breast cancer; second primary cancer; progression during neo-adjuvant treatment; or death from any cause). Par. who experienced progression during treatment and were withdrawn were considered to have a DFS event at withdrawal.
| Percentage | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| Percentage of Participants (Par.) With Disease-free Survival (DFS) at the End of 5 Years From Randomization | 90 (72 to 97) | 67 (47 to 80) | 66 (44 to 82) |
12-lead ECGs were performed, and participants were classified as having normal ECG, abnormal- not clinically significant (NCS) ECG, and abnormal-clinically significant (CS) ECG per investigator opinion and reported result.
| participants | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| Baseline, Normal, n= 28, 32, 30 | 18 | 23 | 23 |
| Baseline, Abnormal-NCS, n= 28, 32, 30 | 10 | 8 | 7 |
| Baseline, Abnormal-CS, n= 28, 32, 30 | 0 | 1 | 0 |
| EOT/early withdrawal, Normal, n= 16, 21, 16 | 10 | 12 | 12 |
| EOT/early withdrawal, Abnormal-NCS, n= 16, 21, 16 | 6 | 8 | 4 |
| EOT/early withdrawal, Abnormal-CS, n= 16, 21, 16 | 0 | 1 | 0 |
LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function. LVEF was measured by performing echocardiogram (ECHO). If ECHO could not be performed or if the investigator believed that it was not conclusive to evaluate LVEF, then a multigated acquisition (MUGA) scan was performed.
| participants | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| Week 3, n= 30, 31, 26 | 1 | 0 | 1 |
| Week 9, n= 30, 32, 27 | 1 | 0 | 1 |
| Week 15, n= 31, 34, 28 | 1 | 2 | 2 |
| Early withdrawal/EOT, n= 31, 34, 28 | 1 | 4 | 2 |
| 3-month survival follow-up, n= 31, 34, 28 | 2 | 4 | 3 |
| 6-month survival follow-up, n= 31, 34, 28 | 4 | 4 | 4 |
Expression (exp) of biomarker proteins (prot) were analyzed to determine if individual prot levels either in the Baseline or Day 14 breast tumor biopsy specimen correlated with breast pCR. A biomarker indicates a change in exp or state of a prot that correlates with the risk or disease progression, or with the susceptibility of the disease to a given treatment. Biomarkers are characteristic biological properties that can be detected and measured in parts of the body like blood or tissue. pCR=yes: participants (par.) had breast pCR. pCR=no: par. did not have breast pCR. Prot exp values are represented as normalized, scaled values; the unit of measurement is unit-less. Raw exp values were processed as follows: background subtraction of the raw exp value, then that value divided by beta-acting exp to normalize the exp value. A Standard Z score was calculated to scale the exp value.
| : normalized relative expression level | Trastuzumab | Lapatinib |
|---|---|---|
| Baseline, EGFR_Tyr1068; pCR=yes, n=0, 4 | NA ± NA | -0.70 ± 0.47 |
| Baseline, Baseline, EGFR_Tyr1068; pCR=no, n=0, 11 | NA ± NA | 0.05 ± 0.55 |
| Post Baseline, EGFR_Tyr1068; pCR=yes, n=9, 0 | 0.65 ± 1.02 | NA ± NA |
| Post Baseline, EGFR_Tyr1068; pCR=no, n=6, 0 | -0.26 ± 0.56 | NA ± NA |
| Day 14, pSTAT5; pCR=yes, n=11, 6 | NA ± NA | NA ± NA |
| Day 14, pSTAT5; pCR=no, n=9, 11 | NA ± NA | NA ± NA |
| Post Baseline, PI3K; pCR=yes, n=0, 5 | NA ± NA | 0.46 ± 0.73 |
| Post Baseline, PI3K; pCR=no, n=0, 10 | NA ± NA | -0.53 ± 0.67 |
| Post Baseline, LC3B; pCR=yes, n=0, 5 | NA ± NA | 0.68 ± 0.81 |
| Post Baseline, LC3B; pCR=no, n=0, 10 | NA ± NA | -0.43 ± 0.75 |
| Post Baseline, MMP9; pCR=yes, n=0, 5 | NA ± NA | 0.71 ± 0.34 |
| Post Baseline, MMP9; pCR=no, n=0, 5 | NA ± NA | -0.48 ± 0.48 |
| Post Baseline, GSK3_a_b_Tyr279_216; pCR=yes, n=8,0 | 0.26 ± 0.82 | NA ± NA |
| Post Baseline, GSK3_a_b_Tyr279_216; pCR=no, n=5,0 | -0.86 ± 0.67 | NA ± NA |
Stem cell data were of poor quality and thus could not be analyzed. Increases or decreases in cancer stem cells and how the changes correlated with response/non-response to treatment were to have been assessed.
No measurements were reported for this outcome.
Transcriptional data were of poor quality and thus could not be analyzed. Gene pathways that correlate with response/non-response to treatment were to have been evaluated. The unit of measure is unit less; however, the processed values would be considered normalized relative expression level.
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Trastuzumab | — | 7/32 (21.9%) | 31/32 (96.9%) |
| Lapatinib | — | 7/34 (20.6%) | 34/34 (100%) |
| Trastuzumab+Lapatinib | — | 8/31 (25.8%) | 31/31 (100%) |
| Event | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| Febrile nuetropeniaBlood and lymphatic system disorders | 3/32 | 0/34 | 2/31 |
| NeutropeniaBlood and lymphatic system disorders | 3/32 | 0/34 | 1/31 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 3/32 | 0/34 | 1/31 |
| PyrexiaGeneral disorders | 0/32 | 3/34 | 0/31 |
| DiarrhoeaGastrointestinal disorders | 0/32 | 2/34 | 2/31 |
| GastroenteritisInfections and infestations | 0/32 | 0/34 | 1/31 |
| Urinary tract infectionInfections and infestations | 0/32 | 0/34 | 1/31 |
| VomitingGastrointestinal disorders | 0/32 | 1/34 | 1/31 |
| NauseaGastrointestinal disorders | 0/32 | 0/34 | 1/31 |
| StomatitisGastrointestinal disorders | 0/32 | 0/34 | 1/31 |
| Event | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib |
|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 17/32 | 29/34 | 31/31 |
| NauseaGastrointestinal disorders | 26/32 | 26/34 | 26/31 |
| RashSkin and subcutaneous tissue disorders | 14/32 | 28/34 | 26/31 |
| FatigueGeneral disorders | 22/32 | 24/34 | 24/31 |
| AlopeciaSkin and subcutaneous tissue disorders | 21/32 | 24/34 | 18/31 |
| Neuropathy peripheralNervous system disorders | 15/32 | 19/34 | 14/31 |
| NeutropeniaBlood and lymphatic system disorders | 13/32 | 12/34 | 15/31 |
| VomitingGastrointestinal disorders | 7/32 | 15/34 | 8/31 |
| AnemiaBlood and lymphatic system disorders | 10/32 | 12/34 | 12/31 |
| ConstipationGastrointestinal disorders | 12/32 | 8/34 | 6/31 |
| Age, Continuous(Years) | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib | Total |
|---|---|---|---|---|
| Mean | 51.1 ± 10.90 | 50.8 ± 8.76 | 49.2 ± 10.47 | 50.4 ± 10.01 |
| Sex: Female, Male(Participants) | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib | Total |
|---|---|---|---|---|
| Female | 33 | 34 | 33 | 100 |
| Male | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(participants) | Trastuzumab | Lapatinib | Trastuzumab+Lapatinib | Total |
|---|---|---|---|---|
| African American/African heritage | 8 | 1 | 2 | 11 |
| American Indian or Alaska native | 0 | 0 | 1 | 1 |
| Asian - Central/South Asian heritage | 0 | 1 | 0 | 1 |
| Asian - East Asian heritage | 0 | 1 | 0 | 1 |
| Asian - South East Asian heritage | 0 | 2 | 1 | 3 |
| White - Arabic/North African heritage | 0 | 1 | 0 | 1 |
| White - White/Caucasian/European heritage | 25 | 27 | 29 | 81 |
| Mixed race | 0 | 1 | 0 | 1 |
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GlaxoSmithKline