Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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.

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.

LCL161 was available as 300 mg, tablets, which was supplied in child-resistant bottles.

LCL161

Commercially available paclitaxel was sourced locally by each study site. Generic paclitaxel could be used for study treatment.

iv 80mg/m2

paclitaxel

Novartis Pharmaceuticals

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.

A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer

A Phase II Multi-center, Open-label, Neoadjuvant, Randomized Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer

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.

To assess the number of patients who experienced a pathological response in breast.

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.

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.

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.

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.

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.

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.

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

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

To evaluate the PK of LCL161 when given in combination with paclitaxel.

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.

To evaluate the PK of LCL161 when given in combination with 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.

LCL161+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.

PACLITAXEL

Paclitaxel With LCL161

Paclitaxel Without LCL161

Total

Age, Continuous

< 65 years

>= 65 years

Age, Customized

Sex: Female, Male

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.

Study Director

Patients randomized to the experimental arm for gene expression signature positive 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.

LCL161 + Paclitaxel (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.

Paclitaxel Only (Gene Expression Signature Positive)

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.

LCL161 + Paclitaxel (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.

Paclitaxel Only (Gene Expression Signature Negative)

Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy

Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy

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.

Difference in pCR Rates Between Treatment Arms

Patients randomized to the experimental arm who received LCL161 1800 mg once weekly + paclitaxel 80 mg/m2 weekly for 12 weeks.

LCL161 + Paclitaxel

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)

Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors

Patients randomized to the control arm who received paclitaxel 80 mg/m2 weekly for 12 weeks.

Paclitaxel Only

Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors

Patients randomized to the experimental arm received LCL161 1800 mg once weekly + paclitaxel 80 mg/m2 weekly for 12 weeks.

pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status

pCR Rate in Breast, Regional Nodes and Axilla

Breast Conserving Surgery

Mastectomy

No Surgery

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.

Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery

EAS1-Baseline (n: 20, 16, 21, 22)

EAS1 Post-Baseline (n: 20, 16, 21, 22)

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.

Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS1

EAS2-Baseline (n: 13, 11, 28, 27)

EAS2 Post-Baseline (n:13, 11, 28, 27)

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.

Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS2

Cycle 1 Day 1 (n:97)

Cycle 4 Day 15 (n:47)

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.

Pharmacokinetics (PK) Parameters of LCL161 Only for Cmax

Patients randomized to the LCL161 1800 mg once weekly for 12 weeks.

Pharmacokinetics (PK) Parameters of LCL161 Only for Tmax

Pharmacokinetics (PK) Parameters of LCL161 Only for AUClast

Paclitaxel With LCL161 (Positive Group)

Paclitaxel Without LCL161 (Positive 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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer	NCT01617668	Breast Cancer	LCL161 paclitaxel	18 Years -	Novartis
A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer	NCT01617668	Breast Cancer	LCL161 paclitaxel	18 Years -	Novartis

Spots Global Cancer Trial Database for lcl161,

Every month we try and update this database with for lcl161, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lcl161,

Every month we try and update this database with for lcl161, cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lcl161, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.