Sarilumab + Capecitabine for Breast Cancer

(EMPOWER Trial)

Recruiting at 3 trial locations

Overseen By Kimberly Arieli, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Florida

Must not be taking: Live vaccines

Disqualifiers: Pregnancy, Hepatitis B, Tuberculosis, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination of sarilumab (Kevzara, an immunotherapy drug) and capecitabine (Xeloda, a chemotherapy drug) for people with triple-negative breast cancer (TNBC). The goal is to target any remaining cancer cells after initial treatment, which may improve survival chances and potentially increase the cure rate for this aggressive cancer. The trial includes different groups: one aims to find the right dose for those with advanced TNBC, while another examines the treatment for those with early-stage TNBC who didn’t fully respond to initial chemotherapy. Individuals with TNBC that did not completely respond to chemotherapy and still have cancer present might be a good fit for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, any previous chemotherapy must have been completed at least 3 weeks before starting the study drugs, and prior capecitabine is allowed only if it wasn't part of the treatment right before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using sarilumab and capecitabine together might be safe and manageable for patients with certain types of breast cancer, such as HER2-negative metastatic breast cancer and triple-negative breast cancer (TNBC). Previous studies did not reveal any new safety issues, which is encouraging. However, some patients experienced side effects, including serious ones. While most people handled the treatment well, there remains a chance of side effects. Anyone considering joining a trial should discuss these risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy treatments for breast cancer, sarilumab offers a novel approach by targeting the immune system, specifically the interleukin-6 (IL-6) receptor. This could potentially reduce inflammation and enhance the cancer-fighting effects of capecitabine, a chemotherapy drug. Researchers are excited about this combination because it might boost the effectiveness against tough cases like metastatic triple-negative breast cancer (TNBC) and hormone-resistant types, where traditional therapies often fall short. By pairing an immune-modulating drug with chemotherapy, this treatment could open new doors for patients with limited options.

What evidence suggests that sarilumab plus capecitabine could be an effective treatment for triple negative breast cancer?

Studies have shown that capecitabine effectively treats triple negative breast cancer (TNBC), particularly in patients who haven't fully responded to initial treatments. This trial will explore one arm combining sarilumab with capecitabine, which has shown promise in treating HER2 negative metastatic breast cancer, including TNBC. This combination aims to target and eliminate small numbers of cancer cells that might remain after treatment, potentially improving survival rates. Early findings suggest this combination could be safe and tolerable. The research explores whether adding sarilumab can enhance capecitabine's effectiveness against this aggressive cancer type. ^{1 2 4 5 6}

Who Is on the Research Team?

Priya Jayachandran, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for adults with metastatic triple negative or hormone resistant, Her2/neu-negative breast cancer. They must have a life expectancy of at least 6 months, not be pregnant or breastfeeding, and agree to use effective contraception. No prior treatment with capecitabine or sarilumab is allowed except in neoadjuvant regimens.

Inclusion Criteria

My breast cancer is triple negative or hormone resistant and Her2 negative.

I haven't had systemic treatment for breast cancer, except as part of a neoadjuvant regimen that didn't include capecitabine or sarilumab.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I don't have any health conditions that would make the study treatment unsafe for me.

I have a history of diverticulitis.

I have had a tuberculosis injection in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose finding study of sarilumab plus capecitabine in patients with metastatic TNBC and metastatic HER2/neu-negative and hormone resistant breast cancer. A total of 4 doses of sarilumab will be given with the starting dose of 150 mg SQ at 3-weeks cycles given 3 days prior to each of the first 4 of 8 cycles of capecitabine.

9 weeks

Visits every 3 weeks

Phase II Treatment

Single arm study in Stage I to III TNBC with less than a complete pCR after neoadjuvant therapy evaluating the combination of sarilumab with capecitabine. There are 8 cycles of capecitabine, with the first 4 cycles combined with sarilumab.

14 weeks

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Sarilumab

Trial Overview The study tests Sarilumab combined with Capecitabine on patients who still have minimal residual disease after standard treatments for aggressive triple negative breast cancer. The goal is to improve survival by eliminating this remaining disease.

How Is the Trial Designed?

Group I: Phase 2 single arm study Experimental Treatment 2 Interventions

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

Group II: Parallel Baseline Arm Experimental Treatment 1 Intervention

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.

Group III: Experimental: Phase I Experimental Treatment 2 Interventions

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

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Capecitabine (Xeloda) is an oral chemotherapy that delivers 5-FU directly to tumors, offering superior response rates and equivalent survival outcomes compared to intravenous 5-FU in first-line metastatic colorectal cancer (MCRC).

Capecitabine has a favorable safety profile, with manageable side effects like hand-foot syndrome and diarrhea, allowing for prompt dose adjustments without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. Sternberg, CN., Reichardt, P., Holland, M.[2015]

A retrospective study of 12 patients with severe renal impairment (GFR <30 mL/min) showed that capecitabine can be safely administered with close monitoring and dose adjustments, despite previous contraindications from the manufacturer based on a small Phase II trial.

Most patients experienced only mild to moderate adverse effects, and some showed a positive response to treatment, indicating that capecitabine may still be effective in this population when managed carefully.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR Jhaveri, KD., Flombaum, C., Shah, M., et al.[2022]

A study involving 44 cancer patients (20 Japanese and 24 Caucasian) found no significant differences in the pharmacokinetics of capecitabine and its key metabolites, indicating that the drug behaves similarly in both populations.

While Caucasian patients showed higher plasma concentrations of alpha-fluoro-beta-alanine (FBAL), this difference is not clinically relevant since FBAL does not have antiproliferative activity and does not affect the tolerability of capecitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of capecitabine (Xeloda) in Japanese and Caucasian patients with breast cancer. Reigner, B., Watanabe, T., Schüller, J., et al.[2022]

In a study of 19 colorectal cancer patients, capecitabine was shown to preferentially convert to 5-fluorouracil (5-FU) in tumor tissues, with 5-FU concentrations in tumors being 3.2 times higher than in adjacent healthy tissues, indicating effective targeting of the drug.

The enzyme thymidine phosphorylase (TP) plays a crucial role in this preferential activation, being significantly more active in colorectal tumors compared to healthy tissue, which helps explain the enhanced efficacy of capecitabine in treating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Schüller, J., Cassidy, J., Dumont, E., et al.[2022]

Capecitabine is a well-tolerated treatment for metastatic breast cancer, showing minimal side effects like myelosuppression and hair loss, which makes it a promising option for combination therapies with other anticancer drugs.

Ongoing phase II/III trials are investigating the use of capecitabine in early breast cancer treatment, and preliminary results indicate that it may provide significant benefits when used as part of adjuvant and neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. Fumoleau, P., Cameron, D.[2019]

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

Xeloda (capecitabine) is an effective oral treatment for metastatic breast cancer patients who have not responded to anthracycline and paclitaxel chemotherapy, showing a 20% overall response rate in a phase II trial with 163 patients and a median survival of 12.8 months.

Xeloda is well tolerated, with common side effects including hand-foot syndrome and nausea, and it has demonstrated higher response rates compared to paclitaxel and cyclophosphamide/methotrexate/5-FU in additional studies, making it a valuable option for patients with limited treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xeloda in the treatment of metastatic breast cancer. Blum, JL.[2017]

In a study of 42 patients with advanced breast and colorectal cancer, capecitabine showed a partial response rate of 29.16% for breast cancer and 11.76% for colorectal cancer, indicating its potential efficacy in these pretreated patients.

Capecitabine was well tolerated with low toxicity levels, as most adverse reactions were mild, although 7.14% of patients experienced grade 3 hand-foot syndrome, and hypertriglyceridemia was noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. Stathopoulos, GP., Koutantos, J., Lazaki, H., et al.[2022]

Capecitabine is an oral pro-drug of fluorouracil that has been approved by the FDA as a first-line treatment for metastatic colorectal cancer and for use in metastatic breast cancer patients who are resistant to other treatments.

The drug has shown improved tolerability and comparable efficacy to intravenous fluorouracil, making it a convenient and effective option for treating various carcinomas, including prostate, pancreatic, renal cell, and ovarian cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Koukourakis, GV., Kouloulias, V., Koukourakis, MJ., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04333706

Study Details | A Dose Finding Phase 1 of Sarilumab Plus ... A dose finding study of sarilumab plus capecitabine in patients with metastatic TNBC and metastatic HER2/neu-negative and hormone resistant breast cancer.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01735

Sarilumab plus Capecitabine for the Treatment of HER2 ... Sarilumab with capecitabine may be safe, tolerable and effective in treating patients with HER2 negative metastatic breast cancer and stage I-III TNBC with high ...

3. trialx.com trialx.com/clinical-trials/listings/242073/a-dose-finding-phase-1-of-sarilumab-plus-capecitabine-in-her2neu-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-d/?&geo_lat=33.930293&geo_lng=-118.2114603&radius=10&place=Lynwood&user_country=United%20States

A Dose Finding Phase 1 of Sarilumab Plus Capecitabine ... This study looks to advance a novel and potent strategy to eliminate minimal residual disease (MRD) in triple negative breast cancer (TNBC) ...

4. go.drugbank.com go.drugbank.com/drugs/DB11767/clinical_trials?conditions=DBCOND0029766%2CDBCOND0020966%2CDBCOND0023541%2CDBCOND0071771&phase=1&purpose=treatment&status=recruiting

Sarilumab Recruiting Phase 1 Trials for Triple Negative / ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7057426/

Phase II study of pembrolizumab and capecitabine for triple ... We conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10723519/

Adjuvant nivolumab, capecitabine or the combination in ... Although no new safety signals were identified in the combination arm, the incidence of drug-related adverse events, including grade 3, was higher in the ...