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

NCT ID: NCT01617668

Last Updated: 2016-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 209 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2014-09-30

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

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

LCL161

Intervention Type: DRUG

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

paclitaxel

Intervention Type: DRUG

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

iv 80mg/m2

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.

Group Type: ACTIVE_COMPARATOR

paclitaxel

Intervention Type: DRUG

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

iv 80mg/m2

Interventions

LCL161

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

Intervention Type: DRUG

paclitaxel

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

iv 80mg/m2

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, United States

Cedars Sinai Medical Center SC

Los Angeles, California, United States

University of California at Los Angeles UCLA SC

Los Angeles, California, United States

Stanford University Medical Center Stanford

Stanford, California, United States

Yale University School of Medicine Yale Univ

New Haven, Connecticut, United States

H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC

Tampa, Florida, United States

Massachusetts General Hospital Mass General 2

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center Dept Onc

New York, New York, United States

Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State

Columbus, Ohio, United States

Vanderbilt University Medical Center Vanderbilt - Thompson Ln

Nashville, Tennessee, United States

Baylor College of Medicine Dept of Oncology

Houston, Texas, United States

Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(5)

San Antonio, Texas, United States

University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 2

Madison, Wisconsin, United States

Novartis Investigative Site

Nedlands, Western Australia, Australia

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Itajaí, Santa Catarina, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Brno, , Czechia

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Olomouc, , Czechia

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Berlin, , Germany

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Düsseldorf, , Germany

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Erlangen, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Freiburg im Breisgau, , Germany

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Heidelberg, , Germany

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Kiel, , Germany

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Lübeck, , Germany

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München, , Germany

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Dublin, Ireland, Ireland

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Dublin, , Ireland

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Padua, PD, Italy

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Seoul, Korea, South Korea

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Seoul, Korea, South Korea

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Seville, Andalusia, Spain

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Barcelona, Catalonia, Spain

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Santiago de Compostela, Galicia, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Valencia, Valencia, Spain

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Valencia, Valencia, Spain

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Taipei, Taiwan, Taiwan

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Taipei, Taiwan, ROC, Taiwan

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Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan

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Brighton, East Sussex, United Kingdom

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Kingston upon Thames, Surrey, United Kingdom

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Sutton, Surrey, United Kingdom

Novartis Investigative Site

London, , United Kingdom

Countries

United States; Australia; Brazil; Czechia; Germany; Ireland; Italy; Russia; South Korea; Spain; Taiwan; United Kingdom

Other Identifiers

2012-000677-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLCL161A2201

Identifier Type: -

Identifier Source: org_study_id