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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01617668
First received: May 30, 2012
Last updated: July 19, 2016
Last verified: July 2016
Results First Received: September 18, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: LCL161
Drug: paclitaxel

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.
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.
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.
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.

Participant Flow:   Overall Study
    Paclitaxel With LCL161 (Positive Group)     Paclitaxel Without LCL161 (Positive Group)     Paclitaxel With LCL161 (Negative Group)     Paclitaxel Without LCL161 (Negative Group)  
STARTED     51     50 [1]   55     53 [2]
Randomized Patients     51     54     55     55  
COMPLETED     38     41     32     38  
NOT COMPLETED     13     9     23     15  
Adverse Event                 7                 0                 12                 5  
Physician Decision                 1                 2                 3                 0  
Progressive Disease                 4                 4                 6                 9  
Subject/guardian decision                 1                 3                 2                 1  
[1] 54 patients were randomized and only 50 received study treatment.
[2] 55 patients were randomized and only 53 received study treatment.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.
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.
Total Total of all reporting groups

Baseline Measures
    Paclitaxel With LCL161     Paclitaxel Without LCL161     Total  
Number of Participants  
[units: participants]
  106     103     209  
Age  
[units: Years]
Mean (Standard Deviation)
  48.6  (10.14)     48.7  (9.98)     48.7  (10.04)  
Age, Customized  
[units: Participants]
     
< 65 years     98     96     194  
>= 65 years     8     7     15  
Gender  
[units: Participants]
     
Female     106     103     209  
Male     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy   [ Time Frame: 12 weeks ]

2.  Primary:   Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy   [ Time Frame: 12 weeks ]

3.  Primary:   Difference in pCR Rates Between Treatment Arms   [ Time Frame: 12 weeks ]

4.  Secondary:   Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors   [ Time Frame: 12 weeks ]

5.  Secondary:   Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors   [ Time Frame: 12 weeks ]

6.  Secondary:   pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status   [ Time Frame: 12 weeks ]

7.  Secondary:   pCR Rate in Breast, Regional Nodes and Axilla   [ Time Frame: 12 weeks ]

8.  Secondary:   Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery   [ Time Frame: 16 weeks ]

9.  Secondary:   Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS1   [ Time Frame: Baseline, Post-baeline at Cycle 1, Day 2 (C1D2) or Cycle 1, Day 9 (C1D9) ]

10.  Secondary:   Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS2   [ Time Frame: Baseline, Post-baeline at Cycle 1, Day 2 or Cycle 1, Day 9 ]

11.  Secondary:   Pharmacokinetics (PK) Parameters of LCL161 Only for Cmax   [ Time Frame: cycle 1 day 1, cycle 4 day 15 ]

12.  Secondary:   Pharmacokinetics (PK) Parameters of LCL161 Only for Tmax   [ Time Frame: cycle 1 day 1, cycle 4 day 15 ]

13.  Secondary:   Pharmacokinetics (PK) Parameters of LCL161 Only for AUClast   [ Time Frame: cycle 1 day 1, cycle 4 day 15 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01617668     History of Changes
Other Study ID Numbers: CLCL161A2201
2012-000677-23 ( EudraCT Number )
Study First Received: May 30, 2012
Results First Received: September 18, 2015
Last Updated: July 19, 2016
Health Authority: United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Australia: Department of Health and Ageing Therapeutic Goods Administration
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Turkey: Ministry of Health
Ireland: Irish Medicines Board
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: Ministry of Health
Czech Republic: State Institute for Drug Control
South Korea: Korea Food and Drug Administration (KFDA)
Brazil:: ANVISA - Agência Nacional de Vigilância Sanitária
Germany: Federal Institute for Drugs and Medical Devices
Russia: Ministry of Health of the Russian Federation