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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Capecitabine (Xeloda) for breast cancer?

Capecitabine (Xeloda) is effective in treating metastatic breast cancer, especially in patients who have not responded to other treatments. It is well-tolerated and can be used in combination with other cancer drugs, showing promising results in early breast cancer treatment. ^{1 2 3 4 5}

Is the combination of Sarilumab and Capecitabine safe for humans?

Capecitabine (Xeloda) is generally considered safe for humans, with common side effects including hand-foot syndrome (redness and swelling of the hands and feet), mouth sores, and diarrhea. It is often preferred for its convenience as an oral medication. However, specific safety data for the combination of Sarilumab and Capecitabine is not available in the provided research. ^{3 5 6 7 8}

What makes the drug combination of Sarilumab and Capecitabine unique for breast cancer treatment?

The combination of Sarilumab and Capecitabine is unique because it pairs an immune-modulating drug (Sarilumab) with a chemotherapy drug (Capecitabine) that is activated directly in the tumor, potentially enhancing the treatment's effectiveness while minimizing side effects. This approach is novel as it combines immune system modulation with targeted chemotherapy, which is not a standard treatment for breast cancer. ^{1 4 5 8 9}

Research Team

Priya Jayachandran, MD

Principal Investigator

University of Southern California

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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, 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of capecitabine (Xeloda) in Japanese and Caucasian patients with breast cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. [2022]

6. United States 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. [2022]

7. Scotland pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. [2015]

8. England pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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