A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With LCL161 in Patients With Triple Negative Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01617668
First received: May 30, 2012
Last updated: March 27, 2014
Last verified: March 2014

May 30, 2012
March 27, 2014
August 2012
July 2014   (final data collection date for primary outcome measure)
Pathological complete response (pCR) rate in breast after 12 weeks of therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer, analyzed separately in the gene expression signature negative and positive groups
Pathological complete response (pCR) rate in breast after 12 weeks of therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancers that are positive for a gene expression signature
Complete list of historical versions of study NCT01617668 on ClinicalTrials.gov Archive Site
  • Frequency of adverse events [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    To characterize the safety and tolerability of the LCL161/paclitaxel combination compared to weekly paclitaxel alone
  • Caspase 3 activation in tumor by IHC [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To evaluate whether combination treatment with LCL161 and paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone
  • PK parameters including Area Under Curve (AUC) [ Time Frame: pre-dose, 0.5, 1, 2, 4 hours post-dose ] [ Designated as safety issue: No ]
    To evaluate the PK of LCL161 when given in combination with paclitaxel
  • Rates of breast conserving surgery and mastectomy [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone
  • Clinical response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone
  • Disease response using RECIST 1.1 criteria [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone
  • pCR rate in breast, regional nodes and axilla [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone
  • Frequency of serious adverse events [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    To characterize the safety and tolerability of the LCL161/paclitaxel combination compared to weekly paclitaxel alone
  • Frequency of clinical laboratory abnormalities [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    To characterize the safety and tolerability of the LCL161/paclitaxel combination compared to weekly paclitaxel alone
  • pCR rate after treatment with LCL161 + paclitaxel [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess whether use of the gene expression signature identifies tumors more likely to respond to treatment with LCL161 and paclitaxel
  • PCRrate in breast after 12 weeks of therapy- Full study population [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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
  • PCR rate in breast after 12 weeks of therapy with gene signature + or - treated with paclitaxel alone [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess whether the gene expression signature is correlated with response to single agent paclitaxel
  • Gene expression profiling (whole genome microarray profiling) and pCR rate in breast [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Evaluate whether specific patterns of gene expression correlate with response to LCL161 + paclitaxel and mechanisms of resistance
  • Sequencing of tumor DNA for genetic alterations in cancer relevant genes [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Evaluate whether tumor genotype influences response to treatment with LCL161
  • Frequency of adverse events [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To characterize the safety and tolerability of the LCL161/paclitaxel combination compared to weekly paclitaxel alone
  • Caspase 3 activation in tumor by IHC [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To evaluate whether combination treatment with LCL161 and paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone
  • Area Under Curve (AUC) [ Time Frame: pre-dose, 0.5, 1, 2, 4 hours post-dose ] [ Designated as safety issue: No ]
    To evaluate the PK of LCL161 when given in combination with paclitaxel
  • Rates of breast conserving surgery and mastectomy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone
  • Clinical response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone by physical examination and breast calipers
  • Disease response using RECIST 1.1 criteria [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone
  • pCR rate in breast, regional nodes and axilla [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To assess other indicators of disease response for the LCL161 + paclitaxel combination compared to paclitaxel alone. To confirm histopathological absence of invasive disease in breast.
  • Frequency of serious adverse events [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To characterize the safety and tolerability of the LCL161/paclitaxel combination compared to weekly paclitaxel alone
  • Frequency of clinical laboratory abnormalities [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To characterize the safety and tolerability of the LCL161/paclitaxel combination compared to weekly paclitaxel alone
Not Provided
Not Provided
 
A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With 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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: Paclitaxel + LCL161
  • Drug: paclitaxel
    iv 80mg/m2
  • Experimental: Paclitaxel with LCL161
    Intervention: Drug: Paclitaxel + LCL161
  • Active Comparator: Paclitaxel without LCL161
    Intervention: Drug: paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
July 2014
July 2014   (final data collection date for primary outcome measure)

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

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
Female
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Italy,   Taiwan,   United Kingdom,   Turkey,   Australia,   Belgium,   Brazil,   Czech Republic,   France,   Germany,   Ireland,   Korea, Republic of,   Russian Federation,   Spain
 
NCT01617668
CLCL161A2201, 2012-000677-23
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP