Oral Chemotherapy for Early Stage Breast Cancer

(BRE-08 Trial)

Overseen By Prathmika Jha, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Must not be taking: Warfarin

Disqualifiers: Stage IIIB-IV, Active infection, 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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of an oral chemotherapy combination for treating early-stage breast cancer. The goal is to assess how well Capecitabine, Cyclophosphamide, and Methotrexate work when taken orally. This study suits those with breast cancer that has been surgically removed, is hormone receptor-positive (cancer cells fueled by hormones), and shows no signs of spreading. Participants should have been recommended for chemotherapy by their doctor but should not require other specific targeted therapies simultaneously.

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 significant advancements in breast cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the CMC treatment plan, which includes capecitabine, methotrexate, and cyclophosphamide, has been tested in various situations. In these studies, some side effects have been noted. For instance, when used for early breast cancer, capecitabine has produced varied results. Some people experience side effects, but these are usually manageable.

Participants who took capecitabine reported side effects like hand-foot syndrome (redness and swelling of the hands and feet), diarrhea, and nausea. Methotrexate and cyclophosphamide have also been tested for breast cancer treatment. Common side effects of these drugs include fatigue and low blood cell counts, which can increase infection risk.

Overall, many have found the CMC treatment plan tolerable, although side effects can occur. The current trial is in phase 2, evaluating its safety and effectiveness for treating early-stage breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this oral chemotherapy regimen for early-stage breast cancer because it offers a unique delivery method that could improve patient convenience and adherence. Unlike traditional treatments that often require intravenous administration at a hospital or clinic, this regimen allows patients to take all three drugs—Capecitabine, Cyclophosphamide, and Methotrexate—by mouth at home. This not only reduces the need for frequent hospital visits but also provides a continuous treatment cycle, potentially enhancing the overall effectiveness. The ability to take chemotherapy orally can be a game-changer for many patients, offering a more flexible and less invasive option.

What evidence suggests that this trial's treatments could be effective for early stage breast cancer?

Research has shown that the oral CMC treatment, which includes capecitabine, cyclophosphamide, and methotrexate, is practical and effective for early-stage breast cancer. In this trial, participants will receive the CMC regimen, which studies have found can help prevent cancer recurrence. Capecitabine works well in other treatments, although some standard treatments have demonstrated better survival rates. Cyclophosphamide and methotrexate are well-known cancer treatments that contribute to the regimen's overall success. These findings suggest that the oral CMC treatment could be a promising option for managing early-stage breast cancer. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Cyclophosphamide
• Methotrexate

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Anthracycline-based treatments are effective in reducing relapse risk and extending survival in breast cancer patients, highlighting their importance in management strategies.

The combination of capecitabine and docetaxel has shown significant efficacy and tolerability in metastatic breast cancer, with flexible dosing options that help manage side effects without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and docetaxel combination for the treatment of breast cancer. Morishita, M., Leonard, RC.[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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28600210/

Accelerated versus standard epirubicin followed by ... Background: Adjuvant chemotherapy for early breast cancer has improved outcomes but causes toxicity. The UK TACT2 trial used a 2×2 factorial design to test two ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS616

Assessing the feasibility and cost-effectiveness of all oral ... Methods: This is a Phase II, single arm, non-randomized study enrolling 25 patients with high-risk early-stage HR+ HER2- breast cancer to ...

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00460-6/fulltext

Accelerated versus standard epirubicin followed by ... Adjuvant chemotherapy for patients with early breast cancer improves outcomes but its toxicity affects patients' quality of life (QOL).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6900836/

Randomized Trial of Standard Adjuvant Chemotherapy ... Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine.

5. clinical-breast-cancer.com clinical-breast-cancer.com/article/S1526-8209(11)70911-9/fulltext

A Dose-Finding, Feasibility, and Efficacy Study The data of our study show that cyclophosphamide/methotrexate/capecitabine is feasible and active. The capecitabine dose of 1850 mg/m2 orally on days 1-14 every ...

6. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30404-7/fulltext

Accelerated versus standard epirubicin followed by ... Adjuvant chemotherapy for early breast cancer has improved outcomes but causes toxicity. The UK TACT2 trial used a 2×2 factorial design to ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)54292-2/fulltext

Randomized, open-label, phase II trial of oral capecitabine ... Randomized, open-label, phase II trial of oral capecitabine (Xeloda®) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11697835/

Randomized, open-label, phase II trial of oral capecitabine ... Median time to disease progression was 4.1 months with capecitabine and 3.0 months with CME. Survival was similar in the two treatment groups (median 19.6 ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0959804917307906

Capecitabine in early breast cancer: A meta-analysis of ... Capecitabine is an effective therapy for metastatic breast cancer. Its role in early breast cancer is uncertain due to conflicting data from randomised ...