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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000677-23 | EudraCT Number |
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To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer whose tumors are positive for a defined pattern of gene expression
This is a phase 2, randomized, two-arm, open-label, neoadjuvant, multicenter study in newly diagnosed women with triple-negative breast cancer. Eligible patients will be limited to those with clinical stages T2, N0-N2, M0.
For those patients with triple-negative disease identified on diagnostic biopsy, the presence or absence of the gene expression signature will be determined in a molecular pre-screening phase using the diagnostic biopsy material; patients with TNBC that are positive and negative for the gene expression signature will be eligible for enrollment.
Following a Screening/baseline period to determine eligibility, patients will be randomized to either paclitaxel 80 mg/m2 IV given weekly (the control arm) or paclitaxel 80 mg/m2 IV weekly immediately followed by LCL161 1800 mg PO once weekly (the experimental arm). Enrollment on these arms will be balanced within regions of the world and are stratified 1:1 for gene expression signature status. Treatment will be administered each week for 12 weeks (4 cycles). The length of each treatment cycle is 21 days.
A total of 200 patients will be enrolled and treated, 100 patients in each treatment arm of the study; each arm will contain 50 patients with gene expression signature positive disease and 50 patients with gene expression signature negative disease.
An interim analysis is planned for this study when approximately 50 patients with gene expression signature positive disease have been treated and have either completed the study and have undergone surgery, or have permanently discontinued study treatment for any reason.
For all patients, a tumor biopsy will be performed approximately 24 hours after the first or second dose of study treatment (paclitaxel or paclitaxel + LCL161) to compare the extent of apoptosis in tumor treated with control or experimental therapy. Patients will be scheduled for breast-conserving surgery or mastectomy 15 weeks plus a window of not more than 1 week from the date the subject receives her first treatment (no more than 16 weeks after first treatment). All treated patients are planned to undergo surgery. However, to evaluate the presence of persistent disease those patients with apparent substantial residual or progressive disease or who do not undergo surgery for any reason must have a core needle biopsy of the primary tumor after completing study treatment. At the completion of study treatment, patients are expected to continue post-operative treatment with a standard anthracycline-based chemotherapy regimen such as FAC (5-FU/doxorubicin/cyclophosphamide), FEC (5-FU/epirubicin/cyclophosphamide) or AC (doxorubicin/cyclophosphamide). The specific regimen will be chosen by the treating physician.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Paclitaxel with LCL161 | Experimental | Patients randomized to the experimental arm received paclitaxel 80 mg/m2 weekly + LECL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
| Paclitaxel without LCL161 | Active Comparator | Patients randomized to the control arm received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LCL161 | Drug | LCL161 was available as 300 mg, tablets, which was supplied in child-resistant bottles. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy | pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on Bayesian design using a binomial distribution for the data with a beta prior. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). Median values are posterior medians of pCR rate for each group. | 12 weeks |
| Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy | To assess the number of patients who experienced a pathological response in breast. | 12 weeks |
| Difference in pCR Rates Between Treatment Arms | pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on the posterior distribution of the difference in pCR rates between the experimental and control arms of the study, within each gene expression signature group.The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors | To assess whether use of the gene expression signature identifies tumors more likely to respond to treatment with LCL161 and paclitaxel. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Highlands Oncology Group Dept of Highlands Oncology Grp | Fayetteville | Arkansas | 72703 | United States | ||
Only 50 of 54 pts in the Paclitaxel without LCL161 (Positive group) received study drug; Only 53 of 55 pts in the Paclitaxel without LCL161 (Negative group) received study drug.
215 patients were randomized to receive the study treatment. 105 gene expression signature positive patients were randomized to LCL161+paclitaxel (N=51) or paclitaxel only (N=54). 110 gene expression signature negative patients were randomized to LCL161+paclitaxel (N=55) or paclitaxel only (N=55).
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| ID | Title | Description |
|---|---|---|
| FG000 | Paclitaxel With LCL161 (Positive Group) | Patients randomized to the experimental arm received paclitaxel 80 mg/m2 weekly + LECL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| paclitaxel | Drug | Commercially available paclitaxel was sourced locally by each study site. Generic paclitaxel could be used for study treatment. iv 80mg/m2 |
|
| 12 weeks |
| Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors | To assess whether use of the gene expression signature identifies tumors more likely to respond to treatment with paclitaxel only. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | 12 weeks |
| pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status | To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer regardless of tumor gene expression signature status. This comparison is between the 2 study treatments, regardless of gene signature status. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | 12 weeks |
| pCR Rate in Breast, Regional Nodes and Axilla | To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone. The pCR in breast, regional nodes, and axilla were determined based on the America Joint Committee on Cancer Staging [AJCC] stages T1c, T2, N0-N2, M0) were (AJCC) pathologic staging recorded on the eCRF: a patient was considered to be a responder in breast, regional nodes, and axilla if the pathological complete response was reported for breast and if the regional lymph nodes staging was pN0 (including i-, mol-, mol+).The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | 12 weeks |
| Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery | To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone. Rates of breast conserving surgery and mastectomy also contributed to the overall assessment of disease response and were summarized by treatment arm within each gene expression signature status. For this analysis, patients with multicentric breast cancer were excluded, as all patients in this group were expected to be treated with mastectomy. | 16 weeks |
| Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS1 | To evaluate whether combination treatment with LCL161 and paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone. To evaluate whether combination treatment with LCL161 and paclitaxel was associated with increased apoptosis compared to weekly paclitaxel alone, cleaved caspase 3 activation in tumor by IHC was examined. Gene expression signature status is derived based on continuous gene expression signature score using cut-off 0.6661 (positive: score ≥ 0.6661; negative: score <0.6661); cycle = 28 days; each patient had either C1D2 or C1D9 | Baseline, Post-baeline at Cycle 1, Day 2 (C1D2) or Cycle 1, Day 9 (C1D9) |
| Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS2 | To evaluate whether combination treatment with LCL161 and paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone. To evaluate whether combination treatment with LCL161 and paclitaxel was associated with increased apoptosis compared to weekly paclitaxel alone, cleaved caspase 3 activation in tumor by IHC was examined. Cycle = 28 days; each patient had either C1D2 or C1D9 | Baseline, Post-baeline at Cycle 1, Day 2 or Cycle 1, Day 9 |
| Pharmacokinetics (PK) Parameters of LCL161 Only for Cmax | To evaluate the PK of LCL161 when given in combination with paclitaxel. | cycle 1 day 1, cycle 4 day 15 |
| Pharmacokinetics (PK) Parameters of LCL161 Only for Tmax | To evaluate the PK of LCL161 when given in combination with paclitaxel. The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data for LCL161. | cycle 1 day 1, cycle 4 day 15 |
| Pharmacokinetics (PK) Parameters of LCL161 Only for AUClast | To evaluate the PK of LCL161 when given in combination with paclitaxel | cycle 1 day 1, cycle 4 day 15 |
| Cedars Sinai Medical Center SC |
| Los Angeles |
| California |
| 90048 |
| United States |
| University of California at Los Angeles UCLA SC | Los Angeles | California | 90095 | United States |
| Stanford University Medical Center Stanford | Stanford | California | 94304 | United States |
| Yale University School of Medicine Yale Univ | New Haven | Connecticut | 06520 | United States |
| H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC | Tampa | Florida | 33612 | United States |
| Massachusetts General Hospital Mass General 2 | Boston | Massachusetts | 02114 | United States |
| Memorial Sloan Kettering Cancer Center Dept Onc | New York | New York | 90033 | United States |
| Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State | Columbus | Ohio | 43210 | United States |
| Vanderbilt University Medical Center Vanderbilt - Thompson Ln | Nashville | Tennessee | 37232 | United States |
| Baylor College of Medicine Dept of Oncology | Houston | Texas | 77030 | United States |
| Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(5) | San Antonio | Texas | 78229 | United States |
| University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 2 | Madison | Wisconsin | 53792-6164 | United States |
| Novartis Investigative Site | Nedlands | Western Australia | 6009 | Australia |
| Novartis Investigative Site | Itajaí | Santa Catarina | 88301-229 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 01317-002 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 01323-900 | Brazil |
| Novartis Investigative Site | Brno | 65653 | Czechia |
| Novartis Investigative Site | Olomouc | 775 20 | Czechia |
| Novartis Investigative Site | Berlin | 13125 | Germany |
| Novartis Investigative Site | Düsseldorf | 40235 | Germany |
| Novartis Investigative Site | Erlangen | 91054 | Germany |
| Novartis Investigative Site | Essen | 45136 | Germany |
| Novartis Investigative Site | Frankfurt | 60389 | Germany |
| Novartis Investigative Site | Freiburg im Breisgau | D 79106 | Germany |
| Novartis Investigative Site | Heidelberg | 69120 | Germany |
| Novartis Investigative Site | Kiel | 24105 | Germany |
| Novartis Investigative Site | Lübeck | 23538 | Germany |
| Novartis Investigative Site | München | 81675 | Germany |
| Novartis Investigative Site | Dublin | Ireland | Ireland |
| Novartis Investigative Site | Dublin | 9 | Ireland |
| Novartis Investigative Site | Padova | PD | 35100 | Italy |
| Novartis Investigative Site | Saint Petersburg | 191104 | Russia |
| Novartis Investigative Site | Saint Petersburg | 197758 | Russia |
| Novartis Investigative Site | Seoul | Korea | 03080 | South Korea |
| Novartis Investigative Site | Seoul | Korea | 05505 | South Korea |
| Novartis Investigative Site | Seville | Andalusia | 41013 | Spain |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | Santiago de Compostela | Galicia | 15706 | Spain |
| Novartis Investigative Site | Madrid | Madrid | 28041 | Spain |
| Novartis Investigative Site | Madrid | Madrid | 28050 | Spain |
| Novartis Investigative Site | Valencia | Valencia | 46009 | Spain |
| Novartis Investigative Site | Valencia | Valencia | 46010 | Spain |
| Novartis Investigative Site | Taipei | Taiwan | 10002 | Taiwan |
| Novartis Investigative Site | Taipei | Taiwan, ROC | 112 | Taiwan |
| Novartis Investigative Site | Kuei-Shan Chiang | Taoyuan/ Taiwan ROC | 33305 | Taiwan |
| Novartis Investigative Site | Brighton | East Sussex | BN2 5BE | United Kingdom |
| Novartis Investigative Site | Kingston upon Thames | Surrey | KT2 7QB | United Kingdom |
| Novartis Investigative Site | Sutton | Surrey | SM2 5PT | United Kingdom |
| Novartis Investigative Site | London | SW3 6JJ | United Kingdom |
| Paclitaxel Without LCL161 (Positive Group) |
Patients randomized to the control arm received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| FG002 | Paclitaxel With LCL161 (Negative Group) | Patients randomized to the experimental arm received paclitaxel 80 mg/m2 weekly + LCL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| FG003 | Paclitaxel Without LCL161 (Negative Group) | Patients randomized to the control arm received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| Randomized Patients |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The Full Analysis Set (FAS) was composed of all patients who received at least one full or partial dose of LCL161 + paclitaxel or one full or partial dose of paclitaxel alone.
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| ID | Title | Description |
|---|---|---|
| BG000 | Paclitaxel With LCL161 | Patients randomized to the experimental arm received paclitaxel 80 mg/m2 weekly + LECL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| BG001 | Paclitaxel Without LCL161 | Patients randomized to the control arm received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Age, Customized | Number | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy | pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on Bayesian design using a binomial distribution for the data with a beta prior. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). Median values are posterior medians of pCR rate for each group. | The Full Analysis Set (FAS) was composed of all patients who received at least one full or partial dose of LCL161 + paclitaxel or one full or partial dose of paclitaxel alone. | Posted | Median | 95% Confidence Interval | Percentage of Participants | 12 weeks |
|
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| Primary | Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy | To assess the number of patients who experienced a pathological response in breast. | The Full Analysis Set (FAS) was composed of all patients who received at least one full or partial dose of LCL161 + paclitaxel or one full or partial dose of paclitaxel alone. | Posted | Number | Participants | 12 weeks |
| |||||||||||||||||||||||||||||||||||||
| Primary | Difference in pCR Rates Between Treatment Arms | pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on the posterior distribution of the difference in pCR rates between the experimental and control arms of the study, within each gene expression signature group.The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | FAS are patients who received at least 1 full or partial dose of LCL161 + paclitaxel or 1 full or partial dose of paclitaxel alone. These values are medians of posterior distribution of difference of pCR rate between treatment arms based on a Bayesian model. 95% Confidence interval is actually 95% credible interval. | Posted | Median | 95% Confidence Interval | Difference in percentage of participants | 12 weeks |
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| Secondary | Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors | To assess whether use of the gene expression signature identifies tumors more likely to respond to treatment with LCL161 and paclitaxel. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | Efficacy Analysis Set 1 (EAS1) are patients who received at least 1 full or partial dose of LCL161 + paclitaxel or of paclitaxel alone with a valid gene expression signature score. Gene expression signature status is derived based on continuous gene expression signature score using cut-off 0.6661(positive: score ≥ 0.6661; negative: score <0.6661) | Posted | Median | 95% Confidence Interval | Difference in percentage of participants | 12 weeks |
|
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| Secondary | Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors | To assess whether use of the gene expression signature identifies tumors more likely to respond to treatment with paclitaxel only. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | Efficacy Analysis Set 1 (EAS1) are patients who received at least 1 full or partial dose of LCL161 + paclitaxel or of paclitaxel alone with a valid gene expression signature score. Gene expression signature status is derived based on continuous gene expression signature score using cut-off 0.6661(positive: score ≥ 0.6661; negative: score <0.6661) | Posted | Median | 95% Confidence Interval | Difference in percentage of participants | 12 weeks |
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| Secondary | pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status | To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer regardless of tumor gene expression signature status. This comparison is between the 2 study treatments, regardless of gene signature status. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | Efficacy Analysis Set 1 (EAS1) are patients who received at least 1 full or partial dose of LCL161 + paclitaxel or of paclitaxel alone with a valid gene expression signature score. Gene expression signature status is derived based on continuous gene expression signature score using cut-off 0.6661(positive: score ≥ 0.6661; negative: score <0.6661) | Posted | Median | 95% Confidence Interval | Percentage of participants | 12 weeks |
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| Secondary | pCR Rate in Breast, Regional Nodes and Axilla | To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone. The pCR in breast, regional nodes, and axilla were determined based on the America Joint Committee on Cancer Staging [AJCC] stages T1c, T2, N0-N2, M0) were (AJCC) pathologic staging recorded on the eCRF: a patient was considered to be a responder in breast, regional nodes, and axilla if the pathological complete response was reported for breast and if the regional lymph nodes staging was pN0 (including i-, mol-, mol+).The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval. | Efficacy Analysis Set 1 (EAS1) are patients who received at least 1 full or partial dose of LCL161 + paclitaxel or of paclitaxel alone with a valid gene expression signature score. Gene expression signature status is derived based on continuous gene expression signature score using cut-off 0.6661(positive: score ≥ 0.6661; negative: score <0.6661) | Posted | Median | 95% Confidence Interval | Percentage of participants | 12 weeks |
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| Secondary | Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery | To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone. Rates of breast conserving surgery and mastectomy also contributed to the overall assessment of disease response and were summarized by treatment arm within each gene expression signature status. For this analysis, patients with multicentric breast cancer were excluded, as all patients in this group were expected to be treated with mastectomy. | EAS1 - patients receiving at least 1 full or partial dose of LCL161 + paclitaxel or of paclitaxel alone with a valid gene expression signature (GES) score. GES status is derived based on continuous GES score using cut-off 0.6661(pos: score ≥ 0.6661; neg: score <0.6661). Patients with multicentric breast cancer were excluded. | Posted | Number | Percentage of participants | 16 weeks |
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| Secondary | Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS1 | To evaluate whether combination treatment with LCL161 and paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone. To evaluate whether combination treatment with LCL161 and paclitaxel was associated with increased apoptosis compared to weekly paclitaxel alone, cleaved caspase 3 activation in tumor by IHC was examined. Gene expression signature status is derived based on continuous gene expression signature score using cut-off 0.6661 (positive: score ≥ 0.6661; negative: score <0.6661); cycle = 28 days; each patient had either C1D2 or C1D9 | Efficacy Analysis Set 1 (EAS1) is patients (pts) who received at least 1 full or partial dose of LCL161 + paclitaxel or of paclitaxel alone with valid gene expression signature score. All pts were considered for analysis (N). Only pts (n) with baseline & post baseline values for the given time point were analyzed for that time point. | Posted | Mean | Standard Deviation | % of positive tumor cells | Baseline, Post-baeline at Cycle 1, Day 2 (C1D2) or Cycle 1, Day 9 (C1D9) |
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| Secondary | Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS2 | To evaluate whether combination treatment with LCL161 and paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone. To evaluate whether combination treatment with LCL161 and paclitaxel was associated with increased apoptosis compared to weekly paclitaxel alone, cleaved caspase 3 activation in tumor by IHC was examined. Cycle = 28 days; each patient had either C1D2 or C1D9 | The Efficacy Analysis Set 2 (EAS2) was the same as EAS1 except that the threshold for classifying a patient into the positive gene group was 0.7716. All the EAS2 set participants were considered for the analysis (N). Only participants (n) who had baseline and post baseline values for the given time point were analyzed for that time point. | Posted | Mean | Standard Deviation | % of positive tumor cells | Baseline, Post-baeline at Cycle 1, Day 2 or Cycle 1, Day 9 |
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| Secondary | Pharmacokinetics (PK) Parameters of LCL161 Only for Cmax | To evaluate the PK of LCL161 when given in combination with paclitaxel. | The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data for LCL161. Only sparse/limited PK samples were collected and analyzed. | Posted | Median | Full Range | ng/mL | cycle 1 day 1, cycle 4 day 15 |
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| Secondary | Pharmacokinetics (PK) Parameters of LCL161 Only for Tmax | To evaluate the PK of LCL161 when given in combination with paclitaxel. The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data for LCL161. | The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data for LCL161. Only sparse/limited PK samples were collected and analyzed. | Posted | Median | Full Range | h | cycle 1 day 1, cycle 4 day 15 |
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| Secondary | Pharmacokinetics (PK) Parameters of LCL161 Only for AUClast | To evaluate the PK of LCL161 when given in combination with paclitaxel | The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data for LCL161. Only sparse/limited PK samples were collected and analyzed. | Posted | Median | Full Range | ng*hr/mL | cycle 1 day 1, cycle 4 day 15 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LCL161+PACLITAXEL | Patients randomized to the experimental arm for gene expression signature positive/negative received LCL161 1800 mg once weekly + paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. | 45 | 106 | 106 | 106 | ||
| EG001 | PACLITAXEL | Patients randomized to the control arm for gene expression signature positive/negative received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. | 7 | 103 | 101 | 103 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 17.0 | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | 17.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | 17.0 | Systematic Assessment |
| |
| Lymph node pain | Blood and lymphatic system disorders | 17.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | 17.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | 17.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Chills | General disorders | 17.0 | Systematic Assessment |
| |
| Feeling cold | General disorders | 17.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | 17.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | 17.0 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | 17.0 | Systematic Assessment |
| |
| Anaphylactic shock | Immune system disorders | 17.0 | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | 17.0 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | 17.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | 17.0 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Febrile infection | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Infection | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | 17.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | 17.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | 17.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | 17.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | 17.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | 17.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | 17.0 | Systematic Assessment |
| |
| Polyarthritis | Musculoskeletal and connective tissue disorders | 17.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | 17.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | 17.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Immobile | Social circumstances | 17.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | 17.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 17.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | 17.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | 17.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | 17.0 | Systematic Assessment |
| |
| Asthenia | General disorders | 17.0 | Systematic Assessment |
| |
| Chills | General disorders | 17.0 | Systematic Assessment |
| |
| Fatigue | General disorders | 17.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | 17.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | 17.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | 17.0 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | 17.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | 17.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | 17.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | 17.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | 17.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | 17.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | 17.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | 17.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | 17.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | 17.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | 17.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | 17.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 17.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 17.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | 17.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 17.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | 17.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | 17.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | 17.0 | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | 17.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Palmar-Plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
| |
| Flushing | Vascular disorders | 17.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | 17.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | 17.0 | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | trialandresults.registries@novartis.com |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C574246 | LCL161 |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
Not provided
Not provided
| >= 65 years |
|
| Male |
|
| OG003 | Paclitaxel Only (Gene Expression Signature Negative) | Patients randomized to the control arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
|
Patients randomized to the control arm for gene expression signature positive received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG002 | LCL161 + Paclitaxel (Gene Expression Signature Negative) | Patients randomized to the experimental arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly + LCL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG003 | Paclitaxel Only (Gene Expression Signature Negative) | Patients randomized to the control arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Paclitaxel Only (Gene Expression Signature Positive) |
Patients randomized to the control arm for gene expression signature positive received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG002 | LCL161 + Paclitaxel (Gene Expression Signature Negative) | Patients randomized to the experimental arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly + LCL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG003 | Paclitaxel Only (Gene Expression Signature Negative) | Patients randomized to the control arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
|
| OG002 | LCL161 + Paclitaxel (Gene Expression Signature Negative) | Patients randomized to the experimental arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly + LCL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG003 | Paclitaxel Only (Gene Expression Signature Negative) | Patients randomized to the control arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
|
Patients randomized to the control arm for gene expression signature positive received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG002 | LCL161 + Paclitaxel (Gene Expression Signature Negative) | Patients randomized to the experimental arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly + LCL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG003 | Paclitaxel Only (Gene Expression Signature Negative) | Patients randomized to the control arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
|
| OG002 | LCL161 + Paclitaxel (Gene Expression Signature Negative) | Patients randomized to the experimental arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly + LCL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
| OG003 | Paclitaxel Only (Gene Expression Signature Negative) | Patients randomized to the control arm for gene expression signature negative received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. |
|
|
|
|
|