A Dose Finding Phase 1 of Sarilumab Plus Capecitabine in HER2/Neu-Negative Metastatic Breast Cancer and a Single-arm, Historically-controlled Phase 2 Study of Sarilumab Plus Capecitabine in Stage I-III Triple Negative Breast Cancer With High-Risk Residual Disease (EMPOWER)

NCT04333706 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 1B-22-3HS-23-000191R01CA238387-01A1
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 3

Brief Summary

This study looks to advance a novel and potent strategy to eliminate minimal residual disease (MRD) in triple negative breast cancer (TNBC) present even after multimodal treatment, thereby improving survival and increasing cure rate in this aggressive cancer. Patients with locally advanced TNBC are at high risk of developing lethal metastatic disease within 2 years of diagnosis, especially for those without a pathologic complete response (pCR) after neoadjuvant chemotherapy. The high risk occurs despite surgical excision of the primary tumor and axillary lymph nodes to eliminate residual disease.

Conditions

Breast; Metastatic; Triple Negative; Cancer; Disseminated Tumor Cell

Outcome Measures

Primary Outcomes (3)

• Phase I: Maximum Tolerated Dose (MTD)

  Establish MTD of sarilumab plus capecitabine in patients with metastatic TNBC and metastatic HER2/neu-negative and hormone resistant breast cancer

  first treatment up to 9 weeks

• Phase I: Dose-limiting toxicity (DLT)

  Defined events that are possibly, probably, or definitely related to the study treatment:

  first treatment up to 9 weeks

• Phase II:To determine the percent of patients with positive CTCs and DTCs (if available) becoming negative CTCs and DTCs (if available) after treatment

  Bone marrow aspirates will be performed before treatment and at defined time points during treatment.

  baseline up to 14 weeks

Study Arms (3)

Experimental: Phase I

EXPERIMENTAL

A dose finding study of sarilumab plus capecitabine in patients with metastatic TNBC and metastatic HER2/neu-negative and hormone resistant breast cancer.

Combination Product: Sarilumab 150mg or 200 mg plus Capecitabine; Combination Product: Sarilumab 150mg plus Capecitabine

Phase 2 single arm study

EXPERIMENTAL

Study of adjuvant sarilumab plus capecitabine in stage I to III TNBC with less than a pCR

Combination Product: Sarilumab 150mg or 200 mg plus Capecitabine; Combination Product: Sarilumab 150mg plus Capecitabine

Parallel Baseline Arm

OTHER

Study of standard adjuvant capecitabine in stage I to III TNBC with less than a pCR. This Arm will be open in parallel with both Phases 1 and 2. Blood samples will be obtained during the course of the study. Bone marrow samples are optional.

Drug: Capecitabine

Interventions

Capecitabine DRUG

Capecitabine 1000 mg BID

Parallel Baseline Arm

Sarilumab 150mg plus Capecitabine COMBINATION_PRODUCT

Dose escalation schedule of sarilumab. The starting dose for sarilumab is 150 mg SQ every 21 days, given 3 days prior to the first 4 of 8 cycles of capecitabine 1000 mg BID.

Experimental: Phase I; Phase 2 single arm study

Sarilumab 150mg or 200 mg plus Capecitabine COMBINATION_PRODUCT

Sarilumab 150mg or 200 mg plus Capecitabine 1000 mg BID

Experimental: Phase I; Phase 2 single arm study

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Written informed consent obtained from the subject and the ability for the subject to comply with all the study-related procedures.
• B. Both males and females ≥ eighteen years of age
• C. A clinical diagnosis of metastatic triple negative or hormone resistant, Her2/neu-negative breast cancer that has been confirmed histologically at one point during the course of the disease. TNBC is defined as ER/PR IHC positivity rate of \<10% and Her2Neu-negative (Phase I only)
• D. A life expectancy of at least 6 months. (Phase I only)
• E. Any previous cytotoxic chemotherapy must have been a minimum of 3 weeks prior to study drug administration. There is no limit on the number of prior therapies. For ER/PR-positive tumors, endocrine therapy must have been included in at least one of those prior regimens. Prior capecitabine is allowed only if not given in the treatment regimen immediately prior to the enrollment in this study. (Phase I only)
• F. A diagnosis of TNBC confirmed histologically and defined as ER/PR IHC positivity rate of \<10% and Her2/neu-negative. (Phase II and Parallel Baseline Arm only)
• G. A pathologic confirmation of stage I, or II, or III breast cancer with less than a complete pCR, defined as the absence of residual invasive cancer in resected breast specimen and sampled lymph nodes with residual noninvasive cancer or in situ disease allowed. (Phase II and Parallel Baseline Arm only)
• H. Must not have received prior systemic treatment for breast cancer except for those included in the neoadjuvant regimen and the neoadjuvant regimen must not have included capecitabine nor sarilumab. (Phase II and Parallel Baseline Arm only)
• I. An ECOG Performance Status ≤2.
• J. Adequate organ function defined as:
• Absolute neutrophil count (ANC) \> 1500/mcl (use of G-CSF is allowed)
• Platelets ≥ 100,000/mcl
• Hemoglobin ≥ 9 (pRBC +/- ESA are allowed)
• ALT ≤ 5 x ULN
• AST ≤ 5 x ULN

You may not qualify if:

• A. Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 24 weeks after the last dose of study drug.
• B. Females who are pregnant or breastfeeding.
• C. History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
• D. Hepatitis B infection except for prior vaccination. (Phase I and Phase II only).
• E. Known history of tuberculosis injection. (Phase I and Phase II only).
• F. A history of diverticulitis. (Phase I and Phase II only).
• G. Use of live vaccines within 30 days prior to study treatment due to the risk of infection. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella (MMR), varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed. (Phase I and Phase II only)
• H. History of other malignancy that in the primary oncologist's estimation has at the time of study participation a higher risk of recurrence or death than the study-related cancer.
• I. Prisoners or subjects who are involuntarily incarcerated.
• J. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
• K. Subjects demonstrating an inability to comply with the study and/or follow-up procedures.

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

RECRUITING

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

UF Health

Gainesville, Florida, 32610, United States

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

Capecitabine; sarilumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Anastasia Martynova, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimberly Arieli, RN

CONTACT

323-865-3935; Kimberly.Arieli@med.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 3, 2020
• Study Start: September 26, 2020
• Primary Completion (Estimated): November 3, 2026
• Study Completion (Estimated): May 3, 2027
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)