Phase 2
Completed N=209
A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer
Source: ClinicalTrials.gov NCT01617668 ↗Enrolled (actual)
209
Serious AEs
24.9%
Results posted
Aug 2016
Primary outcomePrimary: Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy — 24.9; 23.4; 6.9; 9.1 Percentage of Participants
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy |
24.9; 23.4; 6.9; 9.1 | — |
| PRIMARY Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy |
13; 12; 4; 5 | — |
| PRIMARY Difference in pCR Rates Between Treatment Arms |
1.5; NA; -2.0; NA | — |
| SECONDARY Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors |
18.2 | — |
| SECONDARY Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors |
13.3 | — |
| SECONDARY pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status |
15.5; 15.7 | — |
| SECONDARY pCR Rate in Breast, Regional Nodes and Axilla |
21.5; 19.1; 6.9; 5.5 | — |
| SECONDARY Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery |
60.4; 60.0; 49.0; 44.7; 25.0; 26.7 | — |
| SECONDARY Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS1 |
1.5; 1.4; 1.4; 2.1; 2.6; 2.4 | — |
| SECONDARY Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS2 |
1.3; 1.6; 1.5; 1.9; 2.3; 2.7 | — |
| SECONDARY Pharmacokinetics (PK) Parameters of LCL161 Only for Cmax |
2230.00; 2310.00 | — |
| SECONDARY Pharmacokinetics (PK) Parameters of LCL161 Only for Tmax |
3.72; 3.50 | — |
| SECONDARY Pharmacokinetics (PK) Parameters of LCL161 Only for AUClast |
5250.70; 5522.58 | — |
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
- Other protocol-defined inclusion/exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT01617668). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.