Capecitabine for Breast Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Antiestrogens

Disqualifiers: Pregnancy, Brain metastasis, Heart 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: 5

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests capecitabine, a medication that targets and kills cancer cells, to evaluate its effectiveness in treating a specific type of breast cancer that has spread. The researchers aim to determine if adjusting the dose based on tumor response can better control cancer growth. The trial targets individuals with metastatic breast cancer that is estrogen receptor-positive and HER2-negative. Ideal candidates have this specific type of breast cancer and have not received chemotherapy for their metastatic condition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on antiestrogen treatments like aromatase inhibitors or selective estrogen modulators, you can continue them. Denosumab and zoledronic acid are also allowed as adjunct therapies.

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

Research shows that capecitabine is generally well-tolerated by patients with metastatic breast cancer. Studies have found that lower doses of capecitabine can reduce side effects while still effectively targeting tumors. For example, one study found that taking 1,000 mg/m² twice a day for 14 days, followed by a 7-day break, results in fewer side effects compared to higher doses. Another study confirmed that capecitabine remains safe and effective even for patients who have already tried other treatments. Additionally, taking a fixed dose of capecitabine for 7 days, followed by a 7-day break, showed fewer side effects and worked as well as dosing based on body size.

These findings suggest that capecitabine is a promising option for treating metastatic breast cancer. However, like all medications, it can cause some side effects. Discuss the potential risks and benefits with a healthcare provider before deciding to participate in a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Capecitabine is unique because it is an oral chemotherapy drug that allows patients to take their medication at home, unlike many standard treatments for breast cancer that require intravenous administration at a clinic. This can provide more convenience and flexibility for patients managing their treatment schedules. Additionally, capecitabine is a prodrug, which means it's inactive until it's metabolized in the body, specifically targeting cancer cells and potentially leading to fewer side effects compared to traditional chemotherapy. Researchers are excited about capecitabine because these features could improve patients' quality of life and treatment adherence.

What evidence suggests that capecitabine might be an effective treatment for metastatic breast cancer?

Research shows that capecitabine, which participants in this trial will receive, effectively treats advanced breast cancer. Studies indicate that this medication can significantly improve patient response to treatment and help delay cancer growth. Capecitabine is absorbed by cancer cells and converts into a substance that kills them. This method has demonstrated high success rates in controlling tumors, even in patients with extensive prior treatments. Although it doesn't always increase overall survival time, it effectively slows the disease's progression. ^{3 4 6 7 8}

Who Is on the Research Team?

Lida Mina

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with a type of breast cancer that responds to hormones (ER positive) and lacks the HER2 protein, which has spread beyond its original location. Participants must not have been treated with capecitabine before.

Inclusion Criteria

ALT and AST ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 14 days prior to registration)

My breast cancer is ER+ and HER2-, as confirmed by tests.

Ability to complete questionnaire(s) by themselves or with assistance

Exclusion Criteria

History of severe hypersensitivity reactions to fluorouracil or capecitabine

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

I have not had radiation therapy in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Standard Phase

Patients receive standard dose of capecitabine orally twice daily on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

6 weeks

2 visits (in-person)

Adaptive Phase

Patients receive 50% reduced dose of capecitabine orally twice daily on days 1-14 of each cycle. Dose adjustments are made based on disease burden assessed via CT or blood samples. Cycles repeat every 21 days.

Variable, up to 5 years

Every cycle (in-person), CT every other cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes blood sample collection, CT or MRI, and bone scan if indicated.

Up to 3 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine

Trial Overview The study tests how well capecitabine, an antimetabolite medication that transforms into a substance killing tumor cells, works in controlling metastatic ER positive, HER2 negative breast cancer by adjusting doses based on tumor response.

How Is the Trial Designed?

Group I: Treatment (capecitabine) Experimental Treatment 6 Interventions

See Detailed Description.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

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 (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]

Capecitabine, a chemotherapy drug, can cause adverse effects such as hand-foot syndrome (HFS) and oral hyperpigmentation, particularly in females and individuals with darker skin tones, as highlighted in a case report.

The study emphasizes the need for better recognition and diagnosis of oral hyperpigmentation associated with capecitabine, as its underlying mechanism remains unclear and is not well-documented in existing literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine-induced oral mucosal hyperpigmentation associated with hand-foot syndrome - A literature review. Nascimento, ADAD., Porto, DM., Vidal, AKL.[2023]

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]

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]

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]

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 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]

Citations

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Efficacy and safety of capecitabine-based first-line ... Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS.

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. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625004941

Efficacy of adjuvant capecitabine in triple-negative breast ... Adjuvant capecitabine therapy significantly improved the prognosis of patients with TNBC who had residual disease after NAT.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1612645

Adjuvant Capecitabine for Breast Cancer after ... The addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)63602-1/fulltext

Multicenter phase II study of oral capecitabine (Xeloda“) in ... This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated patients with metastatic breast cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4988831/

A comparison of toxicity profiles between the lower and ... Capecitabine 1,000 mg/m2 bid × 14 days every 21 days (14/21) has been reported to have similar efficacy but more favorable toxicity profile than the approved ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1526820911707923

Safety Profile and Activity of Lower Capecitabine Dose in ... The aim of our study was to confirm safety and activity of capecitabine at lower doses in patients with metastatic breast cancer (MBC).

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3336834/

Capecitabine Monotherapy: Review of Studies in First-Line ... First-line therapy with moderate dose capecitabine in metastatic breast cancer is safe and active: Results of the MONICA trial. Eur J Cancer. 2010;46:3184 ...