Capecitabine for Triple-Negative Breast Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Melinda Telli

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

Must be taking: Capecitabine

Disqualifiers: Metastatic cancer, HIV, Hepatitis, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a blood test to find cancer DNA in patients with a tough type of breast cancer. It helps doctors see if the current treatment is working or if a different one is needed.

Do I need to stop my current medications for the trial?

The trial requires a 4-week period without previous chemotherapy treatment before starting. The protocol does not specify if you need to stop other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Capecitabine for treating triple-negative breast cancer?

Research shows that Capecitabine, when used as a maintenance therapy or in combination with other drugs, has been effective for patients with metastatic triple-negative breast cancer, especially after other treatments have been tried. It is also noted to be well tolerated with minimal side effects. ^{1 2 3 4 5}

Is capecitabine safe for humans?

Capecitabine (also known as Xeloda) is generally well tolerated, but it can cause side effects like hand-foot syndrome (skin reaction on palms and soles), diarrhea, and fatigue. Rarely, it may lead to leukoencephalopathy (a brain condition) in less than one percent of cases. ^{2 6 7 8 9}

How does the drug capecitabine differ from other treatments for triple-negative breast cancer?

Capecitabine is unique because it is an oral drug that becomes active specifically in tumor tissues, converting to 5-fluorouracil (5-FU) directly at the cancer site, which may reduce side effects compared to other treatments. It is particularly used when other treatments like anthracyclines and taxanes have failed, offering a convenient oral administration and a different mechanism of action. ^{1 2 10 11 12}

Research Team

Melinda Telli

Principal Investigator

Stanford Universiy

Eligibility Criteria

This trial is for adults over 18 with early-stage triple-negative breast cancer who've had some chemo but still have disease present. They must be planning to take capecitabine, have good kidney and liver function, not be pregnant or breastfeeding, and agree to use contraception. People with metastatic cancer, HIV, hepatitis B/C, or recent investigational drug use can't join.

Inclusion Criteria

My side effects from previous cancer treatments are mild, except for hair loss and some nerve pain.

My cancer has not spread to other parts of my body.

I am a woman who can have children and I have a negative pregnancy test.

Exclusion Criteria

I am HIV positive or have active hepatitis B or C.

I have not had surgery to completely remove my cancer.

You have taken any experimental drugs within 4 weeks before the study starts.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant capecitabine treatment and are monitored for ctDNA levels

6 months

Every 21 days (in-person)

Follow-up

Participants are monitored for relapse-free survival and overall survival

5 years

Treatment Details

Interventions

• Capecitabine (Anti-metabolites)

Trial Overview The study tests if monitoring ctDNA levels in the blood can predict the effectiveness of capecitabine treatment in preventing breast cancer relapse. It involves regular 'liquid biopsies' during treatment to see how ctDNA changes correlate with tumor genetics.

Participant Groups

Group I: Capecitabine Experimental Treatment 1 Intervention

1000 mg/m2 administered on Days 1 to 14 of 21-day cycles

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Findings from Research

Cisplatin and capecitabine combination therapy showed a response rate of 62.1% in 29 patients with metastatic triple negative breast cancer (TNBC) who had previously progressed after other treatments, indicating its efficacy as a subsequent treatment option.

The therapy was generally well-tolerated, with most side effects being mild to moderate, although some patients experienced significant toxicities such as neutropenia and leukocytopenia, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment]. Li, Q., Xu, B., Li, Q., et al.[2018]

Capecitabine is an effective oral prodrug for treating triple-negative breast cancer (TNBC), converting to 5-fluorouracil preferentially in tumors, and is generally well tolerated with minimal side effects.

In a case report of a 34-year-old woman, capecitabine caused rare neurotoxicity (leukoencephalopathy), which resolved after discontinuation of the drug, highlighting the importance of early detection and prompt management of such side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine-induced leukoencephalopathy in a patient with triple-negative breast cancer: A case report and review of the literature. Liu, L., Brown, EN., Abu-Shahin, FI.[2022]

Capecitabine maintenance therapy (MT) significantly prolongs progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (mTNBC) after initial treatment with capecitabine plus docetaxel, with median PFS of 10.1 months for the MT group compared to 6.7 months for the non-MT group.

The safety profile of capecitabine MT is favorable, as adverse events such as hematologic toxicity and gastrointestinal issues were not significantly different between the maintenance and non-maintenance treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine maintenance therapy for XT chemotherapy-sensitive patients with metastatic triple-negative breast cancer. Liang, X., Di, L., Song, G., et al.[2020]

A meta-analysis of seven randomized clinical trials involving 3151 early-stage triple-negative breast cancer (TNBC) patients showed that adding capecitabine to standard chemotherapy significantly improved disease-free survival (DFS) with a hazard ratio of 0.77.

The same analysis indicated a significant increase in overall survival (OS) for patients receiving capecitabine, with a hazard ratio of 0.69, suggesting that capecitabine can enhance treatment outcomes for early-stage TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant addition of capecitabine to early-stage triple-negative breast cancer patients receiving standard chemotherapy: a meta-analysis. Li, Y., Zhou, Y., Mao, F., et al.[2020]

Capecitabine maintenance therapy significantly improved progression-free survival (PFS) and overall survival (OS) in patients with non-basal-like metastatic triple-negative breast cancer (mTNBC), with median PFS of 7.3 months compared to 5.7 months in the observation group.

Cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR) status were identified as important prognostic biomarkers, indicating that patients with non-basal-like TNBC could particularly benefit from capecitabine maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prognostic and predictive significance of cytokeratin 5/6 and epidermal growth factor receptor in metastatic triple-negative breast cancer treated with maintenance capecitabine. Zhu, Y., Li, K., Zhang, J., et al.[2022]

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]

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 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]

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 (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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Capecitabine-induced leukoencephalopathy in a patient with triple-negative breast cancer: A case report and review of the literature. [2022]

3. China pubmed.ncbi.nlm.nih.gov

Capecitabine maintenance therapy for XT chemotherapy-sensitive patients with metastatic triple-negative breast cancer. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Adjuvant addition of capecitabine to early-stage triple-negative breast cancer patients receiving standard chemotherapy: a meta-analysis. [2020]

5. China pubmed.ncbi.nlm.nih.gov

The prognostic and predictive significance of cytokeratin 5/6 and epidermal growth factor receptor in metastatic triple-negative breast cancer treated with maintenance capecitabine. [2022]

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

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

7. Spain pubmed.ncbi.nlm.nih.gov

Capecitabine-induced oral mucosal hyperpigmentation associated with hand-foot syndrome - A literature review. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

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

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

11. Japan pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

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