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.
12345Is 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.
678910How 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.
1112131415Eligibility 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.
+18 more
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
+13 more
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: CMC orallyExperimental Treatment3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of IllinoisChicago, IL
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Who Is Running the Clinical Trial?
University of Illinois at ChicagoLead Sponsor
References
Current and planned trials with capecitabine in adjuvant/neoadjuvant therapy of breast cancer. [2015]The demonstration of the activity of capecitabine (Xeloda) in advanced breast cancer and of the ability of capecitabine/docetaxel (Taxotere) to improve tumor response, time to disease progression, and survival in this setting has prompted considerable interest in examining uses of capecitabine in adjuvant and neoadjuvant therapy. Trials are planned to compare capecitabine/docetaxel with docetaxel after AC in the adjuvant and neoadjuvant settings, weekly paclitaxel vs capecitabine/docetaxel followed by fluorouracil (5-FU)/epirubicin (Ellence)/cyclophosphamide and local surgery in both adjuvant and neoadjuvant settings, and AC or cyclophosphamide/methotrexate/5-FU vs single-agent capecitabine in adjuvant therapy of elderly patients with node-positive or high-risk node-negative disease. Results of these trials should provide important information on the range of uses of capecitabine in treating breast cancer.
Xeloda in the treatment of metastatic breast cancer. [2017]There are few treatment options available for patients with metastatic breast cancer who have failed anthracycline- and paclitaxel-based chemotherapy. Xeloda (capecitabine) is a novel selectively tumoractivated fluoropyrimidine carbamate producing clinically active levels of 5-fluorouracil (5-FU) at the tumor site. Xeloda is active in breast cancer and is administered orally. It is the only registered treatment for patients in whom anthracycline and taxoid treatment has failed. In a phase II trial of 163 paclitaxel-refractory patients with metastatic breast cancer, the overall response rate with Xeloda was 20%, with three complete responses, and the median survival was 12.8 months. A total of 20% of patients experienced a Clinical Benefit Response (a composite assessment of clinical benefit). Furthermore, Xeloda was well tolerated; the most common treatment-related adverse events were hand-foot syndrome, diarrhea, nausea, vomiting, and fatigue. Two additional studies of Xeloda in patients with metastatic breast cancer have also been completed. In the first study, patients with anthracycline-resistant metastatic breast cancer received either Xeloda or paclitaxel; the response rates were 36 and 26%, respectively. In the second study, women aged >/=55 years received first-line treatment with either Xeloda or cyclophosphamide/methotrexate/5-FU. The response rates were 25 and 16%, respectively. These studies show that Xeloda is an active agent in the treatment of metastatic breast cancer with the additional advantage of oral administration.
Optimizing chemotherapy for patients with advanced breast cancer. [2017]Chemotherapy is offered to almost all patients with metastatic breast cancer. Optimization of treatment has four major goals: (1) To improve access to chemotherapy. Orally active chemotherapy is an attractive option for those patients when access to hospital is limited by financial considerations, long journeys or patient reluctance. In the past, only alkylating agents (cyclophosphamide, chlorambucil, melphalan) could be administered orally. The activity (first- and second-line) of Xeloda (capecitabine) with limited side effects and the development of oral vinorelbine and anthracyclines should improve access to chemotherapy and also concentrate further interest on treatment with long-term administration of cytotoxic agents. (2) To improve response rates and duration in first-line treatment. Response rates have been increased by the use of combinations of taxoids and anthracyclines and/or alkylating agents and/or fluoropyrimidines (>60-70% with complete remission in 10-15% of patients). There is increasing interest in sequential use of active agents or combinations at their optimal doses. Nevertheless, such 'induction regimen' fail to prolong response duration (rarely longer than 9-12 months). The use of less-toxic maintenance chemotherapy regimens increases response duration and disease-free survival. Such maintenance regimens could be used on an outpatient basis and will be further simplified by the availability of active oral agents such as the novel fluoropyrimidine Xeloda. (3) To increase cure rates. This can only be considered with first-line treatment in selected patients (long disease-free interval, minimal number of visceral sites and ability to tolerate high-dose chemotherapy). The completed studies with high-dose chemotherapy and hematopoietic stem cell support have, in fact, shown only a minimal effect on cure rates. Incorporation of very active agents such as taxoids and use of multicycle high-dose therapy may improve these results. (4) To offer alternative active regimens in second and subsequent metastatic progression. Taxoids, vinorelbine and, more recently, Xeloda all achieve a 20-40% response rate in these situations. The reintroduction of agents previously used for adjuvant or first-line therapy can also be considered.
Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. [2019]As an active and well-tolerated agent in the treatment of metastatic breast cancer, capecitabine (Xeloda, F. Hoffmann-La Roche, Basel, Switzerland) has the potential to confer significant clinical benefits in the primary treatment of breast cancer. The minimal myelosuppression and alopecia associated with capecitabine, together with its potential for synergistic activity with a range of other anticancer therapies, lend support to its use in combination regimens with other commonly used cytotoxic agents. Trials to date show that capecitabine combinations incorporating taxanes, vinorelbine, anthracyclines, and cisplatin are active and well tolerated in the metastatic setting. To more fully explore the clinical utility of capecitabine in early breast cancer, an extensive, worldwide phase II/III program is evaluating capecitabine as a component of adjuvant and neoadjuvant therapy. Results presented to date of the large adjuvant and neoadjuvant trials incorporating capecitabine are encouraging and suggest that women with breast cancer might benefit from the activity of capecitabine early in the disease course.
Capecitabine and docetaxel combination for the treatment of breast cancer. [2018]The management of breast cancer depends on the tumor and patient's characteristics. Anthracycline-based regimens have been proven to decrease the risk of relapse and prolong survival time in breast cancer. Taxanes have been incorporated not only into metastatic breast cancer but also into adjuvant regimens. Capecitabine, an oral fluoropyrimidine carbamate, has good single-agent activity and, together with docetaxel, demonstrated preclinical synergy and a survival benefit in metastatic breast cancer. Recent analyses show that capecitabine/docetaxel dosing flexibility for managing side effects does not compromise efficacy, and define this combination regimen as an important treatment option for its efficacy, tolerability and cost-effectiveness.
[Xeloda (capecetabine) in the treatment of disseminated breast cancer after failure with anthracyclines and taxanes]. [2016]Xeloda (capecetabine) has been tested for efficacy and toxicity in treating disseminated breast cancer after the potential of anthracycline (group 1) chemotherapy, anthracyclines plus taxanes (group 2) was exhausted. The patients included into the study (54) were divided into groups 1 (33) and 2 (21). Apparent response was in 24 and 21%, respectively. The drug may be used both in out-patients and those refractory to anthracycline chemotherapy and anthracyclines plus taxanes due to moderate toxicity, slight myelodepression and absence of alopecia which seldom makes treatment useless.
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]The combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer.
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]The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer.
Taxanes: an overview of the pharmacokinetics and pharmacodynamics. [2023]Paclitaxel and docetaxel have emerged in the last two decades as effective antitumor agents in a variety of malignancies. Paclitaxel is a semisynthetic taxane isolated from bark of the Pacific yew tree. Docetaxel is a semisynthetic taxane derived from the needles of the European yew (Taxus baccata). These compounds bind to tubulin, leading to microtubule stabilization, mitotic arrest and, subsequently, cell death. Plasma clearance of paclitaxel exhibits nonlinear kinetics, which results in a disproportionate change in plasma concentration and area under the curve (AUC) with dose alterations. In contrast, docetaxel has a linear disposition over the dose ranges used clinically, so its concentration changes linearly with changes in the dosage. Premedicating with corticosteroids and histamine H1 and H2 receptor antagonists is advocated prior to paclitaxel administration; prior to docetaxel administration, premedication with corticosteroids is suggested. The taxanes are metabolized in the liver by the cytochrome P-450 enzymes and are eliminated in the bile. The known metabolites are either inactive or less potent than the parent compounds. The toxic effects associated with paclitaxel therapy are mainly neutropenia, peripheral neuropathy, and, rarely, cardiotoxicity. Docetaxel toxicity produces mainly myelosuppression and a cumulative dose fluid retention syndrome. Paclitaxel demonstrates sequence-dependent interactions with cisplatin, cyclophosphamide, and doxorubicin. Docetaxel has shown increased myelosuppression with preceding ifosfamide in a preliminary study. The future holds increasing indications for taxanes in newer combination regimens; consideration of their pharmacologic characteristics is an important aspect of designing and applying new taxane-based treatment regimens.
Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609. [2015]The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. The purpose of this phase II study was to evaluate the efficacy and safety of a monthly XP regimen in patients with metastatic breast cancer (MBC).
Evolving role of oral chemotherapy for the treatment of patients with neoplasms. [2013]The past 20 years has seen an increasing trend toward the use of oral chemotherapy for the treatment of patients with a variety of malignancies. The advantages of oral chemotherapy include lower treatment cost, compared with that of intravenous (i.v.) administration, and more convenient treatment for patients. Several oral drugs are now used routinely for cancer treatment, and others are under investigation. Hormonal agents, such as tamoxifen, flutamide, and megestrol acetate, and antimetabolites, such as hydroxyurea, which are available only in oral formulation, have proven both safe and efficacious. Several other oral drugs, including etoposide and cyclophosphamide, have been shown to be useful and often as effective as their i.v. formulations, and more data on the bioavailability of these agents have become available. In addition, several new and promising oral agents (platinum compounds, fluorinated pyrimidines, topoisomerase I inhibitors, and others) are likely to be introduced into clinical practice in the near future. It is possible that eventually, oral combination chemotherapy will be an accepted and standard approach for the treatment of patients with many types of cancer.
Clinical status of capecitabine in the treatment of breast cancer. [2015]New treatment strategies for advanced breast cancer have focused on both the development of new molecular targets in breast cancer cells, as well as improving the therapeutic index of presently available therapy. The development of capecitabine (Xeloda), a new oral fluoropyrimidine, is an example of a chemotherapy drug that has single-agent activity in heavily pretreated patients with advanced breast cancer, with the added convenience of good oral bioavailability. Capecitabine is an excellent treatment option for patients who require symptom palliation and who prefer oral medications. The discussion that follows reviews the clinical data on the use of capecitabine in advanced breast cancer.
Pharmacology of oral chemotherapy agents. [2018]The abundance of orally formulated chemotherapy agents reflects the expanding role of oral chemotherapy in the care of patients with cancer. Many oral chemotherapy agents have been used for a number of years, and several have been developed recently. Newer agents include the prodrugs capecitabine and temozolomide, the retinoid bexarotene, the immunomodulatory agent thalidomide, the protein kinase inhibitor imatinib, and the epidermal growth factor receptor inhibitors gefitinib and erlotinib. Each agent has unique pharmacologic properties, dosing, and side-effect profiles. This article reviews these agents from a pharmacology perspective.
A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR [2022]Capecitabine (Xeloda) is an orally administered precursor of 5'deoxy-5-fluorouridine, which is a preferentially activated to 5-fluorouracil in tumors. It is used in the treatment of colorectal, gastric, and breast cancers. Based on a single Phase II trial, which included a total of 4 patients with severe renal impairment (GFR
Phase II trial of simple oral therapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: SWOG S0430. [2021]Interest in oral agents for the treatment of metastatic breast cancer (MBC) has increased because many patients prefer oral to i.v. regimens. We evaluated a simple oral combination of capecitabine with cyclophosphamide (CPA) for MBC.