Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01617668
Registration number
NCT01617668
Ethics application status
Date submitted
30/05/2012
Date registered
12/06/2012
Date last updated
17/10/2016
Titles & IDs
Public title
A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer
Query!
Scientific title
A Phase II Multi-center, Open-label, Neoadjuvant, Randomized Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer
Query!
Secondary ID [1]
0
0
2012-000677-23
Query!
Secondary ID [2]
0
0
CLCL161A2201
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Breast Cancer
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Breast
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - LCL161
Treatment: Drugs - paclitaxel
Experimental: 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.
Active Comparator: 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.
Treatment: Drugs: LCL161
LCL161 was available as 300 mg, tablets, which was supplied in child-resistant bottles.
Treatment: Drugs: paclitaxel
Commercially available paclitaxel was sourced locally by each study site. Generic paclitaxel could be used for study treatment.
iv 80mg/m2
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
12 weeks
Query!
Primary outcome [2]
0
0
Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy
Query!
Assessment method [2]
0
0
To assess the number of patients who experienced a pathological response in breast.
Query!
Timepoint [2]
0
0
12 weeks
Query!
Primary outcome [3]
0
0
Difference in pCR Rates Between Treatment Arms
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
12 weeks
Query!
Secondary outcome [1]
0
0
Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
12 weeks
Query!
Secondary outcome [2]
0
0
Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
12 weeks
Query!
Secondary outcome [3]
0
0
pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
12 weeks
Query!
Secondary outcome [4]
0
0
pCR Rate in Breast, Regional Nodes and Axilla
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
12 weeks
Query!
Secondary outcome [5]
0
0
Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
16 weeks
Query!
Secondary outcome [6]
0
0
Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS1
Query!
Assessment method [6]
0
0
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
Query!
Timepoint [6]
0
0
Baseline, Post-baeline at Cycle 1, Day 2 (C1D2) or Cycle 1, Day 9 (C1D9)
Query!
Secondary outcome [7]
0
0
Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS2
Query!
Assessment method [7]
0
0
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
Query!
Timepoint [7]
0
0
Baseline, Post-baeline at Cycle 1, Day 2 or Cycle 1, Day 9
Query!
Secondary outcome [8]
0
0
Pharmacokinetics (PK) Parameters of LCL161 Only for Cmax
Query!
Assessment method [8]
0
0
To evaluate the PK of LCL161 when given in combination with paclitaxel.
Query!
Timepoint [8]
0
0
cycle 1 day 1, cycle 4 day 15
Query!
Secondary outcome [9]
0
0
Pharmacokinetics (PK) Parameters of LCL161 Only for Tmax
Query!
Assessment method [9]
0
0
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.
Query!
Timepoint [9]
0
0
cycle 1 day 1, cycle 4 day 15
Query!
Secondary outcome [10]
0
0
Pharmacokinetics (PK) Parameters of LCL161 Only for AUClast
Query!
Assessment method [10]
0
0
To evaluate the PK of LCL161 when given in combination with paclitaxel
Query!
Timepoint [10]
0
0
cycle 1 day 1, cycle 4 day 15
Query!
Eligibility
Key inclusion criteria
- Histologically confirmed diagnosis of invasive triple negative breast cancer
- Known status for the LCL161 predictive gene expression signature as determined during
molecular pre-screening
- Candidates for mastectomy or breast-conserving surgery
- Primary tumor of greater than 20 mm and less than or equal to 50 mm diameter measured
by imaging (previous Amendment #3 was tumor size greater than 10 mm)
- Regional nodes N0-N2
- Absence of distant metastatic disease
- ECOG performance status 0-1
- Adequate bone marrow function
- Adequate liver function and serum transaminases
- Adequate renal function
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Bilateral or inflammatory breast cancer (bilateral mammography is required during
Screening/baseline); locally recurrent breast cancer
- Patients currently receiving systemic therapy for any other malignancy, or having
received systemic therapy for a malignancy in the preceding 3 months
- Uncontrolled cardiac disease
- Patients who are currently receiving chronic treatment (>3 months) with
corticosteroids at a dose = 10 mg of prednisone (or its glucocorticoid equivalent) per
day (inhaled and topical steroids are allowed), or any other chronic immunosuppressive
treatment that cannot be discontinued prior to starting study drug
- Impaired GI function that may affect the absorption of LCL161
- Pregnant or breast feeding (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 180 days after study treatment
- Other protocol-defined inclusion/exclusion criteria may apply
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/08/2012
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/09/2014
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
209
Query!
Recruitment in Australia
Recruitment state(s)
WA
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Nedlands
Query!
Recruitment postcode(s) [1]
0
0
6009 - Nedlands
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Arkansas
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Connecticut
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Florida
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Massachusetts
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
New York
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Ohio
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Tennessee
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Texas
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Wisconsin
Query!
Country [11]
0
0
Brazil
Query!
State/province [11]
0
0
SC
Query!
Country [12]
0
0
Brazil
Query!
State/province [12]
0
0
SP
Query!
Country [13]
0
0
Czech Republic
Query!
State/province [13]
0
0
Brno
Query!
Country [14]
0
0
Czech Republic
Query!
State/province [14]
0
0
Olomouc
Query!
Country [15]
0
0
Germany
Query!
State/province [15]
0
0
Berlin
Query!
Country [16]
0
0
Germany
Query!
State/province [16]
0
0
Düsseldorf
Query!
Country [17]
0
0
Germany
Query!
State/province [17]
0
0
Erlangen
Query!
Country [18]
0
0
Germany
Query!
State/province [18]
0
0
Essen
Query!
Country [19]
0
0
Germany
Query!
State/province [19]
0
0
Frankfurt
Query!
Country [20]
0
0
Germany
Query!
State/province [20]
0
0
Freiburg
Query!
Country [21]
0
0
Germany
Query!
State/province [21]
0
0
Heidelberg
Query!
Country [22]
0
0
Germany
Query!
State/province [22]
0
0
Kiel
Query!
Country [23]
0
0
Germany
Query!
State/province [23]
0
0
Lubeck
Query!
Country [24]
0
0
Germany
Query!
State/province [24]
0
0
München
Query!
Country [25]
0
0
Ireland
Query!
State/province [25]
0
0
Dublin 4
Query!
Country [26]
0
0
Ireland
Query!
State/province [26]
0
0
Dublin
Query!
Country [27]
0
0
Italy
Query!
State/province [27]
0
0
PD
Query!
Country [28]
0
0
Korea, Republic of
Query!
State/province [28]
0
0
Korea
Query!
Country [29]
0
0
Russian Federation
Query!
State/province [29]
0
0
Saint Petersburg
Query!
Country [30]
0
0
Russian Federation
Query!
State/province [30]
0
0
St. Petersburg
Query!
Country [31]
0
0
Spain
Query!
State/province [31]
0
0
Andalucia
Query!
Country [32]
0
0
Spain
Query!
State/province [32]
0
0
Catalunya
Query!
Country [33]
0
0
Spain
Query!
State/province [33]
0
0
Comunidad Valenciana
Query!
Country [34]
0
0
Spain
Query!
State/province [34]
0
0
Galicia
Query!
Country [35]
0
0
Spain
Query!
State/province [35]
0
0
Madrid
Query!
Country [36]
0
0
Taiwan
Query!
State/province [36]
0
0
Taiwan, ROC
Query!
Country [37]
0
0
Taiwan
Query!
State/province [37]
0
0
Taoyuan/ Taiwan ROC
Query!
Country [38]
0
0
Taiwan
Query!
State/province [38]
0
0
Taipei
Query!
Country [39]
0
0
United Kingdom
Query!
State/province [39]
0
0
East Sussex
Query!
Country [40]
0
0
United Kingdom
Query!
State/province [40]
0
0
Surrey
Query!
Country [41]
0
0
United Kingdom
Query!
State/province [41]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
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
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01617668
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01617668
Download to PDF