- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06085742
BRE-08 Phase II Study of CMC Regimen for Early Stage Breast Cancer (BRE-08)
BRE-08: A Phase II Study of an All-Oral Adjuvant Chemotherapy Regimen of Cyclophosphamide, Methotrexate, and Capecitabine (CMC) for Early-Stage Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Participants who require adjuvant radiotherapy for locoregional management may opt to initiate radiotherapy following the fourth cycle of CMC with the final 4 cycles held during radiotherapy. Following completion of radiation therapy, participants may then resume with cycle 5 of CMC. The washout period before and after radiation therapy is a minimum of 2 weeks. Alternatively, patients may receive adjuvant radiotherapy after the completion of the final (8) cycle of CMC.
The study team will collect data on cyclophosphamide, methotrexate, and capecitabine compliance at routine clinical visits every 3 weeks. In addition, standard electrolyte, chemistry and liver function laboratory monitoring will be conducted at each clinic visit
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Prathmika Jha, BS
- Phone Number: 312-413-2746
- Email: pjha7@uic.edu
Study Contact Backup
- Name: Abiola Ibreeheem, MD
- Phone Number: 312-413-1581
- Email: abiolai@uic.edu
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60612
- Recruiting
- University of Illinois
-
Contact:
- Prathmika Jha, BS
- Phone Number: 312-413-2746
- Email: pjha7@uic.edu
-
Contact:
- Abiola R Ibreeheem, MD
- Phone Number: 312-413-1581
- Email: abiolai@uic.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age ≥ 18 years of age at time of consent
- ECOG performance status 0, 1, or 2
- Histologically confirmed invasive breast cancer documented by biopsy or surgical excision.
- Underwent potentially curative resection of primary breast tumor(s) with no gross residual local-regional disease (patients with microscopically positive margins are eligible if adjuvant radiotherapy is planned), with most recent breast or axillary surgery < 120 days prior to date of signed consent.
- No evidence of distant metastatic disease
- Treating Oncologist recommends adjuvant chemotherapy without concurrent biologic/targeted therapy. Patients may receive a CDK4/6 inhibitor after completion of all study treatment, concurrently with adjuvant endocrine therapy. Patients with a germline pathogenic/likely pathogenic variant in a DNA homologous repair gene (e.g. BRCA1, BRCA2, PALB2) may receive adjuvant PARP inhibitor therapy after completion of all study treatment.
- Tumor is estrogen receptor (ER)-positive (> 10% by IHC) and/or progesterone receptor (PR)-positive (> 10% by IHC), HER2-negative by IHC or FISH according to 2018 ASCO-CAP guidelines.
- High risk gene expression profile (either luminal B on MammaPrint/BluePrint, or Recurrence Score > 25 on Oncotype Dx). Study participants are not required to have a high risk gene expression profile if they have a clinical high-risk tumor, defined as:
Age < 50 and any of the following:
- Involvement of 1-3 axillary lymph nodes with metastatic carcinoma (N1mic/N1)
- grade 1 tumor > 3 cm; or grade 2 tumor > 2 cm; or grade 3 tumors > 1 cm (size based on pathological assessment of the maximal dimension of the invasive component of the tumor)
- pT1c-T2 and Ki-67 > 20%
- Presence of lymphovascular invasion
Age > 50 and the following:
Primary tumor > 5 cm (pT3)
• AJCC pathologic stage:
- pT1-2/pN0-1 based on sentinel lymph node biopsy or axillary dissection
stage IIIA (pT3N1 or pT1-3/N2) tumors are eligible . A high risk gene expression profile is not required for pathologic stage IIIA patients.
- Adequate organ function as defined in Table 1. All screening labs to be obtained within 30 days prior to registration.
- Patients with synchronous bilateral primary breast tumors or multiple ipsilateral primary breast tumors are eligible if the treating Oncologist determines that the CMC regimen is appropriate therapy for all primary tumors requiring chemotherapy.
- Able to provide written informed consent and HIPAA authorization for release of personal health information.
- Women of childbearing potential must agree to use 2 methods of birth control, at least one being a barrier form of contraception if they are sexually active with a male partner unless they are considered highly unlikely to conceive as defined in section 8.6, and cannot be pregnant or breast-feeding. A negative serum or urine pregnancy test is required per institutional practice guidelines.
- As determined at the discretion of the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Hematological Leukocytes ≥2,500/mm3 Platelet count ≥ 100,000/mm3 Absolute Neutrophil Count (ANC) ≥ 1,200/mm3 Hemoglobin (Hgb) ≥ 9.0 g/dL Renal Creatinine/Calculated creatinine clearance (CrCl) Cr < 1.5 x upper limit of normal (ULN) or CrCl ≥ 50 mL/min using the Cockcroft-Gault formula Hepatic Bilirubin Bilirubin ≤ 1.5 × ULN. Subjects with Gilbert's syndrome may have a bilirubin > 1.5 × ULN, if no evidence of biliary obstruction exists Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN
Exclusion Criteria:
- Prior cytotoxic chemotherapy for this breast cancer
- Any investigational agents administered during or within 2 weeks prior to start of CMC chemotherapy
- AJCC stage IIIB-IIIC or stage IV
- Active infection requiring systemic therapy
- Uncontrolled HIV/AIDS or active viral hepatitis
- Pregnant or nursing
- Require anticoagulation with warfarin. Anticoagulation with low molecular weight heparins, heparin, or direct oral anticoagulants (DOACs) is permitted.
- Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen, as determined by the treating medical oncologist.
- Any mental or medical condition that prevents the patient from giving informed consent or participating in the trial.
- Other major comorbidity (e.g. advanced cardiopulmonary disease, uncontrolled diabetes mellitus) that may affect the safety or efficacy assessment of this investigational regimen, as determined by study PI
- Inability to swallow pills
- Any medical condition interfering with absorption of oral medications
- Any contraindication for any chemotherapy drug used in the CMC regimen
- Active and ongoing use of medicines known to alter metabolism or tolerability of component drugs in CMC.
- Prisoners
- Unable or unwilling to take a large number of oral pills
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: CMC orally
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
|
60mg/m2 PO once a day (21 continuous days)
10mg/m2 PO BID on days 1, 8, and 15
825mg/m2 PO BID on days 1-14
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relative Dose Intensity (RDI) in patients treated with the CMC regimen. RDI is defined as the sum total of delivered drug in mg/m2/week for each drug in the CMC regimen per the number of participants that have equal to or greater than 85%
Time Frame: 1 year
|
Number of participants that have RDI of the CMC regimen is equal to or greater than 85%
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Invasive Disease Free Survival (iDFS)
Time Frame: 10 years
|
Number of participants that have iDFS, defined as the time from enrollment to documentation of the first of the following: invasive cancer in the ipsilateral breast/chest wall or regional nodes, contralateral invasive breast or regional nodes, distant metastases, or death from any cause |
10 years
|
Distant Disease Free Survival (DDFS)
Time Frame: 10 years
|
Number of participants that have DDFS defined as the time from enrollment to documentation of distant metastases or death from any cause.
|
10 years
|
Overall Survival (OS)
Time Frame: 10 years
|
Number of participants that have OS defined as the time from study enrollment to the date of the subject's death
|
10 years
|
Participant outcomes using the Quality of Life (QOL) and EORTC QOL-C30 questionnaires
Time Frame: 10 years
|
Number of participants having good outcome versus low outcomes.
High score means worse health outcomes and low score means better health outcomes
|
10 years
|
Protocol therapy interruption
Time Frame: 10 years
|
Number of participants that have protocol therapy interruption
|
10 years
|
Discontinuation of protocol therapy
Time Frame: 10 years
|
Number of participants that have discontinuation of protocol therapy
|
10 years
|
Rates of dose reduction of cyclophosphamide
Time Frame: 10 years
|
Number of participants that have dose reduction of cyclophosphamide
|
10 years
|
Rates of dose reduction of methotrexate
Time Frame: 10 years
|
Number of participants that have dose reduction of methotrexate
|
10 years
|
Rates of dose reduction of capecitabine
Time Frame: 10 years
|
Number of participants that have dose reduction of capecitabine
|
10 years
|
Safety of oral CMC regime per the number of participants experiencing adverse events
Time Frame: 1 year
|
Number of participants having adverse event using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5
|
1 year
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Cyclophosphamide
- Capecitabine
- Methotrexate
Other Study ID Numbers
- 2023-0429
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Susan G. Komen Breast Cancer FoundationCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer
Clinical Trials on Cyclophosphamide
-
Children's Hospital Los AngelesLucile Packard Children's HospitalTerminatedMetabolic Diseases | Stem Cell Transplantation | Chronic Granulomatous Disease | Bone Marrow Transplantation | Thalassemia | Wiskott-Aldrich Syndrome | Genetic Diseases | Peripheral Blood Stem Cell Transplantation | Pediatrics | Diamond-Blackfan Anemia | Allogeneic Transplantation | Combined Immune Deficiency | X-linked Lymphoproliferative Disease
-
Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompletedAnemia, AplasticUnited States
-
Columbia UniversityUnknownSevere Combined Immunodeficiency | Fanconi Anemia | Bone Marrow Failure | OsteopetrosisUnited States
-
National Cancer Institute, NaplesImmatics Biotechnologies GmbH; CureVac; European Commission -FP7-Health-2013-Innovation-1CompletedHepatocellular CarcinomaBelgium, Germany, Italy, Spain, United Kingdom
-
Eisai Inc.CompletedBreast Cancer | Ovarian Cancer | Prostate Cancer | Colon Cancer | Renal CancerUnited States
-
Mahidol UniversityTerminatedRenal Insufficiency | InfectionThailand
-
Centre Oscar LambretCompleted
-
Baylor Research InstituteCompletedMalignant Melanoma Stage IVUnited States
-
University of Turin, ItalyUnknown
-
Merck KGaA, Darmstadt, GermanyCompleted