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
  Purpose

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


Condition Intervention Phase
Breast Cancer
Drug: Paclitaxel + LCL161
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 200
Study Start Date: August 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel with LCL161 Drug: Paclitaxel + LCL161
Active Comparator: Paclitaxel without LCL161 Drug: paclitaxel
iv 80mg/m2

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617668

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 71 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01617668     History of Changes
Other Study ID Numbers: CLCL161A2201, 2012-000677-23
Study First Received: May 30, 2012
Last Updated: March 27, 2014
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

Keywords provided by Novartis:
Breast cancer,
LCL161,
paclitaxel,
neoadjuvant,
triple negative breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 29, 2014