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

NCT01617668 | Completed Phase 2 Results

• 2 other identifiers: CLCL161A22012012-000677-23
• Study Type: interventional
• Target: 209
• Locations: 12 countries
• Sites: 50

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

Conditions

Breast Cancer

Keywords

Breast cancer,; LCL161,; paclitaxel,; neoadjuvant,; triple negative breast cancer

Outcome Measures

Primary Outcomes (3)

• Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy

  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.

  12 weeks

• Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy

  To assess the number of patients who experienced a pathological response in breast.

  12 weeks

• Difference in pCR Rates Between Treatment Arms

  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.

  12 weeks

Secondary Outcomes (10)

• Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors

  12 weeks

• Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors

  12 weeks

• pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status

  12 weeks

• pCR Rate in Breast, Regional Nodes and Axilla

  12 weeks

• Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery

  16 weeks

Study Arms (2)

Paclitaxel with LCL161

EXPERIMENTAL

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.

Drug: LCL161; Drug: paclitaxel

Paclitaxel without LCL161

ACTIVE COMPARATOR

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.

Drug: paclitaxel

Interventions

LCL161 DRUG

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

Paclitaxel with LCL161

paclitaxel DRUG

Commercially available paclitaxel was sourced locally by each study site. Generic paclitaxel could be used for study treatment. iv 80mg/m2

Paclitaxel with LCL161; Paclitaxel without LCL161

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (50)

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, 72703, United States

Location

Cedars Sinai Medical Center SC

Los Angeles, California, 90048, United States

Location

University of California at Los Angeles UCLA SC

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center Stanford

Stanford, California, 94304, United States

Location

Yale University School of Medicine Yale Univ

New Haven, Connecticut, 06520, United States

Location

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

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital Mass General 2

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center Dept Onc

New York, New York, 90033, United States

Location

Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State

Columbus, Ohio, 43210, United States

Location

Vanderbilt University Medical Center Vanderbilt - Thompson Ln

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine Dept of Oncology

Houston, Texas, 77030, United States

Location

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

San Antonio, Texas, 78229, United States

Location

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

Madison, Wisconsin, 53792-6164, United States

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Itajaí, Santa Catarina, 88301-229, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01317-002, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01323-900, Brazil

Location

Novartis Investigative Site

Brno, 65653, Czechia

Location

Novartis Investigative Site

Olomouc, 775 20, Czechia

Location

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Düsseldorf, 40235, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Essen, 45136, Germany

Location

Novartis Investigative Site

Frankfurt, 60389, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, D 79106, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Dublin, Ireland, Ireland

Location

Novartis Investigative Site

Dublin, 9, Ireland

Location

Novartis Investigative Site

Padua, PD, 35100, Italy

Location

Novartis Investigative Site

Saint Petersburg, 191104, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197758, Russia

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28041, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28050, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46009, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Taipei, Taiwan, 10002, Taiwan

Location

Novartis Investigative Site

Taipei, Taiwan, ROC, 112, Taiwan

Location

Novartis Investigative Site

Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, 33305, Taiwan

Location

Novartis Investigative Site

Brighton, East Sussex, BN2 5BE, United Kingdom

Location

Novartis Investigative Site

Kingston upon Thames, Surrey, KT2 7QB, United Kingdom

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

LCL161; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2012
• First Posted: June 12, 2012
• Study Start: August 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 17, 2016
• Results First Posted: August 31, 2016

Record last verified: 2016-08

Locations

CZ (2); DE (10); IE (2); AU (1); IT (1); US (13); RU (2); BR (3); TW (3); ES (7); GB (4); KR (2)