Oral Chemotherapy for Early Stage Breast Cancer

(BRE-08 Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Illinois at Chicago

Must not be taking: Warfarin

Disqualifiers: Stage IIIB-IV, Active infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a non-randomized, single arm phase 2 trial of oral CMC based on conversion of doses that would be delivered with conventional metronomic CMF chemotherapy.

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

The trial protocol does not specify if you need to stop your current medications, but it excludes those actively using medicines that alter the metabolism or tolerability of the trial drugs. It's best to discuss your current medications with the trial team.

What evidence supports the effectiveness of the drug Capecitabine (Xeloda) for treating early-stage breast cancer?

Research shows that Capecitabine (Xeloda) is effective in treating advanced breast cancer, with studies indicating it improves tumor response and survival rates. It is also well-tolerated and has shown promise in combination with other drugs for early-stage breast cancer. ^{1 2 3 4 5}

Is oral chemotherapy for early-stage breast cancer safe for humans?

Capecitabine, also known as Xeloda, has been studied for safety in various breast cancer treatments. It generally shows moderate toxicity, meaning it has some side effects but is usually manageable, and it does not commonly cause hair loss. It has been used safely in combination with other drugs for breast cancer treatment. ^{6 7 8 9 10}

How does oral chemotherapy differ from other treatments for early stage breast cancer?

Oral chemotherapy, like capecitabine, offers the convenience of taking medication by mouth instead of through an IV, which can be more comfortable and less costly for patients. This approach is unique because it allows patients to manage their treatment at home, and capecitabine specifically targets cancer cells by converting into an active form within the tumor, potentially reducing side effects. ^{11 12 13 14 15}

Research Team

Eligibility Criteria

This trial is for adults with invasive breast cancer that's been surgically removed, without signs of distant spread. It's specifically for those with high-risk gene profiles or clinical features, and normal organ function. Participants must not be pregnant, able to take oral medication, and willing to use two forms of birth control if applicable.

Inclusion Criteria

Able to provide written informed consent and HIPAA authorization for release of personal health information

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

You have a low level of white blood cells in your blood.

Exclusion Criteria

Pregnant or nursing

You have a serious health condition, such as severe heart or lung disease, or uncontrolled diabetes, that could affect the safety or effectiveness of the study treatment, as determined by the study doctor.

Prisoners

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral CMC regimen consisting of Cyclophosphamide, Methotrexate, and Capecitabine over 8 cycles, with each cycle lasting 3 weeks

24 weeks

Routine clinical visits every 3 weeks

Radiation

Participants may receive adjuvant radiotherapy following the fourth cycle of CMC or after the completion of the final (8th) cycle

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Participants are monitored for long-term outcomes such as Invasive Disease Free Survival, Distant Disease Free Survival, and Overall Survival

10 years

Treatment Details

Interventions

• Capecitabine (Anti-metabolites)
• Cyclophosphamide (Alkylating agents)
• Methotrexate (Anti-metabolites)

Trial Overview The BRE-08 Phase II study tests a chemotherapy combination called CMC (Capecitabine, Cyclophosphamide, Methotrexate) given orally in a non-randomized setting to see its effectiveness in early-stage breast cancer patients who have undergone surgery.

Participant Groups

Group I: CMC orally Experimental Treatment 3 Interventions

All agents in CMC are oral and conform to a 3-week = 1 cycle regimen. All subjects will receive Cyclophosphamide 60mg/m2 PO once a day (21 continuous days) Methotrexate 10mg/m2 PO BID on days 1, 8, and 15 Capecitabine 825mg/m2 PO BID on days 1-14

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Mark I. Rosenblatt

University of Illinois at Chicago

Chief Executive Officer

MD, PhD, MBA, MHA

Jon Radosta

University of Illinois at Chicago

Chief Medical Officer since 2023

MD

Findings from Research

Capecitabine has shown effectiveness in treating advanced breast cancer, particularly when combined with docetaxel, leading to improved tumor response, longer time to disease progression, and better survival rates.

Ongoing trials are set to explore the use of capecitabine in both adjuvant and neoadjuvant therapy, comparing it with other treatment regimens to determine its broader applications in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and planned trials with capecitabine in adjuvant/neoadjuvant therapy of breast cancer. Livingston, R.[2015]

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]

Oral chemotherapy options like Xeloda (capecitabine) and oral vinorelbine improve access for patients with metastatic breast cancer, especially when hospital visits are challenging due to financial or logistical reasons.

Combination therapies using taxoids and anthracyclines have increased response rates in first-line treatments, but maintenance regimens with less toxic agents can prolong response duration and improve disease-free survival, making outpatient treatment more feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing chemotherapy for patients with advanced breast cancer. Marty, M., Espie, M., Cottu, PH., et al.[2017]

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) demonstrated efficacy in treating disseminated breast cancer in patients who had previously exhausted anthracycline and anthracycline plus taxane therapies, with response rates of 24% in group 1 and 21% in group 2.

The treatment was found to have moderate toxicity, with minimal myelodepression and no significant hair loss, making it a viable option for outpatients and those resistant to prior chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Xeloda (capecetabine) in the treatment of disseminated breast cancer after failure with anthracyclines and taxanes]. Semiglazova, TIu., Gershanovich, ML.[2016]

In a clinical trial involving 113 HER2-negative breast cancer patients, the combination of docetaxel and capecitabine (TX regimen) achieved a pathological complete response (pCR) rate of 25.9%, compared to 15.3% for the docetaxel and epirubicin (TE regimen), particularly benefiting patients with high Ki-67 scores.

The TX regimen demonstrated a similar long-term survival rate to the TE regimen while presenting a more manageable toxicity profile, with higher rates of hand-foot syndrome but less alopecia, suggesting it could be a viable anthracycline-free treatment option for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant docetaxel and capecitabine (TX) versus docetaxel and epirubicin (TE) for locally advanced or early her2-negative breast cancer: an open-label, randomized, multi-center, phase II Trial. Yang, H., Xu, L., Guan, S., et al.[2023]

In the JO21095 trial involving 162 patients with HER2-negative metastatic breast cancer, low-dose capecitabine plus docetaxel (XT) demonstrated a superior progression-free survival (PFS) of 10.5 months compared to 9.8 months with single-agent docetaxel, indicating that XT may be a more effective treatment option.

Despite similar rates of severe treatment-related toxicities (grade ≥3) between the two groups, the XT combination had a more manageable safety profile, with fewer instances of fatigue and peripheral edema, suggesting it may be a safer alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Yamamoto, D., Sato, N., Rai, Y., et al.[2018]

Paclitaxel and docetaxel are effective antitumor agents that work by stabilizing microtubules, leading to cell death, but they have different pharmacokinetic profiles; paclitaxel has nonlinear plasma clearance while docetaxel has linear disposition, affecting how their concentrations change with dosage.

Both drugs require premedication to manage side effects, with paclitaxel needing corticosteroids and antihistamines, while docetaxel only requires corticosteroids; their toxic effects differ, with paclitaxel primarily causing neutropenia and peripheral neuropathy, and docetaxel leading to myelosuppression and fluid retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxanes: an overview of the pharmacokinetics and pharmacodynamics. Vaishampayan, U., Parchment, RE., Jasti, BR., et al.[2023]

In a phase II study involving 44 patients with metastatic breast cancer, the combination of capecitabine and paclitaxel (XP) showed an overall response rate of 46.5%, indicating significant antitumor activity.

The treatment was well-tolerated, with manageable side effects, and resulted in a progression-free survival of 8.3 months and overall survival of 22.9 months, making it a viable option for patients with limited prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609. Taguchi, T., Yamamoto, D., Masuda, N., et al.[2015]

Oral chemotherapy has become increasingly popular over the past 20 years due to its lower cost and convenience for patients, making it a practical alternative to intravenous treatments.

Several oral chemotherapy drugs, including hormonal agents and antimetabolites, have been proven safe and effective, with ongoing research suggesting that oral combination therapies may become standard practice for treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of oral chemotherapy for the treatment of patients with neoplasms. Greco, FA.[2013]

Capecitabine (Xeloda) is an effective oral chemotherapy option for patients with advanced breast cancer, particularly those who have already undergone extensive treatment, providing single-agent activity.

The drug offers the convenience of good oral bioavailability, making it suitable for patients seeking symptom relief and preferring oral medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical status of capecitabine in the treatment of breast cancer. Gradishar, WJ.[2015]

Oral chemotherapy agents are increasingly important in cancer treatment, with both long-established and newly developed options available for patients.

Newer oral agents like capecitabine, temozolomide, and imatinib have distinct pharmacologic properties and side effects, highlighting the need for personalized treatment plans based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of oral chemotherapy agents. Birner, A.[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]

In a study of 96 patients with metastatic breast cancer, the combination of capecitabine and cyclophosphamide achieved a response rate of 36% and a median overall survival of 18.8 months, indicating it is an effective treatment option.

The treatment was well-tolerated with mild toxicity and no treatment-related deaths, but the results suggest that single-agent capecitabine may be preferable for prolonging overall survival in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of simple oral therapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: SWOG S0430. Schott, AF., Barlow, WE., Albain, KS., et al.[2021]

References

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

Current and planned trials with capecitabine in adjuvant/neoadjuvant therapy of breast cancer. [2015]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Optimizing chemotherapy for patients with advanced breast cancer. [2017]

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

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

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

Capecitabine and docetaxel combination for the treatment of breast cancer. [2018]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Xeloda (capecetabine) in the treatment of disseminated breast cancer after failure with anthracyclines and taxanes]. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant docetaxel and capecitabine (TX) versus docetaxel and epirubicin (TE) for locally advanced or early her2-negative breast cancer: an open-label, randomized, multi-center, phase II Trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. [2018]

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

Taxanes: an overview of the pharmacokinetics and pharmacodynamics. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609. [2015]

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

Evolving role of oral chemotherapy for the treatment of patients with neoplasms. [2013]

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

Clinical status of capecitabine in the treatment of breast cancer. [2015]

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

Pharmacology of oral chemotherapy agents. [2018]

14. England pubmed.ncbi.nlm.nih.gov

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

15. England pubmed.ncbi.nlm.nih.gov

Phase II trial of simple oral therapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: SWOG S0430. [2021]