Low Dose Capecitabine for Breast Cancer

Overseen By Katia Khoury, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Disqualifiers: Severe hepatic, Renal failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a low dose of capecitabine, a chemotherapy drug, to determine its effectiveness in treating advanced breast cancer with fewer side effects. It targets patients aged 60 or older, or those of any age who are frail and at higher risk of complications from standard treatments. Individuals with HER2-negative breast cancer, who have tried at least one other treatment and can still take pills, may be suitable candidates. The trial seeks to find a safer treatment option for those who might struggle with more aggressive therapies. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing early access to potentially effective therapy.

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, if you are on therapeutic anticoagulation, you should be on a stable dose.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that capecitabine, the drug under study, has been used to treat various cancers, including breast cancer. It is generally considered safe, but like many cancer treatments, it can cause side effects. Studies have found that some patients experience tiredness, diarrhea, and skin reactions on the hands and feet. These side effects are usually manageable but can be uncomfortable.

While capecitabine works well, some patients have experienced more serious side effects, such as a drop in white blood cells, which can lead to infections. However, many patients tolerate the treatment well, especially at lower doses.

Health agencies like the FDA have approved the drug for treating other types of cancer, suggesting it is reasonably safe. This trial tests a lower dose, which might reduce the chance of side effects, especially in older or frail patients. It is important to discuss any concerns with a healthcare provider when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Unlike standard treatments for breast cancer, which often involve higher doses of chemotherapy drugs, this approach uses a low dose of capecitabine, also known as Xeloda, as an oral medication. The low-dose regimen may reduce side effects while maintaining effectiveness, making it potentially more tolerable for patients. Researchers are excited because this could mean fewer hospital visits and a better quality of life for patients, while still effectively managing the cancer.

What evidence suggests that low dose capecitabine might be an effective treatment for advanced breast cancer?

Studies have shown that capecitabine can help treat metastatic breast cancer. Research indicates that even lower doses of this medication can be effective against advanced breast cancer. In this trial, participants will receive a low daily dose of capecitabine. One study found that a low daily dose worked well for patients with advanced HER2-negative breast cancer, meaning the cancer does not have high levels of a protein called HER2. Another study suggested that starting with lower doses might be just as effective as the standard dose. These findings suggest capecitabine could be a promising option for those who might have difficulty with higher doses due to age or health issues. ^{6 7 8 9 10}

Who Is on the Research Team?

Humaria Sarfraz, MD

Principal Investigator

The University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for patients aged ≥60 or frail at any age with advanced breast cancer who have progressed after one treatment line. They must have adequate organ function, HER2 negative status, and either hormone receptor positive or triple-negative breast cancer. Exclusions include HER2 positive cancer, untreated spinal cord compression, prior capecitabine use in metastatic setting, non-measurable disease only, severe liver/renal failure, inability to swallow pills or recent major surgery.

Inclusion Criteria

Patients must be able to provide signed informed consent.

Your bilirubin levels in the blood are not too high. If you have Gilbert disease, your bilirubin levels should be within a certain range.

Your blood clotting tests should be within a certain range if you are not taking blood thinning medication.

Exclusion Criteria

My cancer cannot be measured by standard tests.

I have been treated with Capecitabine for cancer that has spread.

I have not had major surgery in the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low dose capecitabine (1000 mg daily) for advanced breast cancer

12 weeks

Evaluations every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine

Trial Overview

The study tests a low dose of the Capecitabine pill (1000 mg daily) on older or frail patients with advanced breast cancer to see if it's effective and safer than other treatments. It's a phase II single-arm trial where all participants receive the same intervention without comparison groups.

How Is the Trial Designed?

Group I: Low dose capecitabine (Xeloda) Experimental Treatment 1 Intervention

1000 mg capecitabine daily by mouth.

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 Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

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]

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]

Home-based therapy with oral capecitabine offers significant advantages over traditional intravenous chemotherapy, including improved quality of life for patients and cost savings in the treatment of metastatic colorectal cancer.

Capecitabine has been shown to extend survival in patients with previously treated metastatic breast cancer when used in combination with docetaxel, highlighting its effectiveness and cost-efficiency in outpatient settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of capecitabine (Xeloda) for cancer nursing practice. Gerbrecht, BM., Kangas, T.[2015]

Capecitabine is the first oral chemotherapy approved in Canada for treating metastatic breast and colorectal cancer, allowing for home-based administration which requires careful side-effect management by oncology nurses.

While capecitabine is generally well tolerated, it can cause hand-foot syndrome, the most common dose-limiting side effect, necessitating proactive management strategies and patient education to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Canadian experience with capecitabine: partnering with patients to optimize therapy. Gerbrecht, BM.[2019]

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]

The combination of low-dose capecitabine and docetaxel as first-line therapy for anthracycline-pretreated metastatic breast cancer resulted in a 42% response rate and a median overall survival of 23 months among 45 patients studied.

This regimen was well tolerated, with only 11% of patients experiencing grade 3 neutropenia and 7% experiencing grade 3 hand-foot syndrome, suggesting that lower doses of capecitabine may offer a better safety profile while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose capecitabine plus docetaxel as first-line therapy for metastatic breast cancer: phase II results. Michalaki, V., Gennatas, S., Gennatas, K.[2018]

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]

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]

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 (Xeloda) is an effective treatment for advanced/metastatic breast cancer, showing a response rate of 20% in a phase 2 trial with a median survival time of 452 days for patients who were resistant to previous therapies.

The most common side effects reported were hand-foot syndrome and various blood-related issues, indicating that while Capecitabine can be beneficial, it also carries a risk of significant adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral active derivative of fluoropyrimidine. Nishida, M.[2018]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/24899084/

A retrospective study evaluating a fixed low dose ...

We retrospectively analyzed patients treated with a low fixed dose of capecitabine (CAPE-L) at 1,000 mg twice daily for 14 days every 21 days. Outcomes included ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/OA-24-00068

Randomized Trial of Fixed-Dose Capecitabine Compared ...

Oral capecitabine administered for 14 days followed by a 7-day rest period is effective in metastatic breast cancer but results in significant ...

3.

aacrjournals.org

aacrjournals.org/clincancerres/article/31/12_Supplement/P3-10-18/754021/Abstract-P3-10-18-Phase-II-Single-Arm-Trial-of-Low

Phase II Single Arm Trial of Low Dose Capecitabine in ...

This study aims to evaluate both efficacy and tolerability of a daily lower dose of capecitabine in the treatment of advanced HER2-negative breast cancer in ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960977625004941

Efficacy of adjuvant capecitabine in triple-negative breast ...

Capecitabine improved DFS and OS in the HER2-low and stage III populations. •. Capecitabine did not significantly enhance the DFS and OS in the HER2-0 or stage ...

5.

asco.org

asco.org/abstracts-presentations/ABSTRACT93331

Efficacy of low-dose capecitabine in metastatic breast cancer.

Published reports suggest that lower starting doses of cape can be as effective as the approved dose in treating metastatic breast cancer (MBC). We compared ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2022/020896s044s045s046s047s048s049s050s051lbl.pdf

XELODA® (capecitabine) tablets, for oral use

The safety of XELODA in combination with docetaxel was evaluated in patients with metastatic breast cancer in Study SO14999 [see Clinical Studies (14.2)].

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2015/020896s037lbl.pdf

XELODA (capecitabine) tablets, for oral use

The following data are shown for the combination study with XELODA and docetaxel in patients with metastatic breast cancer in Table 7 and Table 8. In the XELODA ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9300946/

Efficacy and Safety of Capecitabine for Triple-Negative ...

Secondary outcomes included the grade 3–5 drug-related adverse events, including neutropenia, diarrhea, fatigue, and hand–foot syndrome. For ...

9.

mayoclinic.org

mayoclinic.org/drugs-supplements/capecitabine-oral-route/description/drg-20062501

Capecitabine (oral route) - Side effects & dosage

Capecitabine is also used together with docetaxel to treat breast cancer ... Safety and efficacy have not been established. Geriatric.

10.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/xeloda

Xeloda | European Medicines Agency (EMA)

Xeloda has been shown to be effective in treating colon, colorectal, gastric and breast cancer. The safety profile of the medicine is considered acceptable. The ...