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BRE-08 Phase II Study of CMC Regimen for Early Stage Breast Cancer (BRE-08)

Primary Purpose

Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Methotrexate
Capecitabine
Sponsored by
University of Illinois at Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of IllinoisRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

CMC orally

Arm Description

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

Outcomes

Primary Outcome Measures

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%
Number of participants that have RDI of the CMC regimen is equal to or greater than 85%

Secondary Outcome Measures

Safety of oral CMC regime per the number of participants experiencing adverse events
Number of participants having adverse event using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5
Invasive Disease Free Survival (iDFS)
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
Distant Disease Free Survival (DDFS)
Number of participants that have DDFS defined as the time from enrollment to documentation of distant metastases or death from any cause.
Overall Survival (OS)
Number of participants that have OS defined as the time from study enrollment to the date of the subject's death
Participant outcomes using the Quality of Life (QOL) and EORTC QOL-C30 questionnaires
Number of participants having good outcome versus low outcomes. High score means worse health outcomes and low score means better health outcomes
Protocol therapy interruption
Number of participants that have protocol therapy interruption
Discontinuation of protocol therapy
Number of participants that have discontinuation of protocol therapy
Rates of dose reduction of cyclophosphamide
Number of participants that have dose reduction of cyclophosphamide
Rates of dose reduction of methotrexate
Number of participants that have dose reduction of methotrexate
Rates of dose reduction of capecitabine
Number of participants that have dose reduction of capecitabine

Full Information

First Posted
October 9, 2023
Last Updated
October 18, 2023
Sponsor
University of Illinois at Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT06085742
Brief Title
BRE-08 Phase II Study of CMC Regimen for Early Stage Breast Cancer
Acronym
BRE-08
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
September 2034 (Anticipated)
Study Completion Date
September 2034 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Illinois at Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CMC orally
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
60mg/m2 PO once a day (21 continuous days)
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
10mg/m2 PO BID on days 1, 8, and 15
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
825mg/m2 PO BID on days 1-14
Primary Outcome Measure Information:
Title
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%
Description
Number of participants that have RDI of the CMC regimen is equal to or greater than 85%
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Safety of oral CMC regime per the number of participants experiencing adverse events
Description
Number of participants having adverse event using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5
Time Frame
1 year
Title
Invasive Disease Free Survival (iDFS)
Description
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
Time Frame
10 years
Title
Distant Disease Free Survival (DDFS)
Description
Number of participants that have DDFS defined as the time from enrollment to documentation of distant metastases or death from any cause.
Time Frame
10 years
Title
Overall Survival (OS)
Description
Number of participants that have OS defined as the time from study enrollment to the date of the subject's death
Time Frame
10 years
Title
Participant outcomes using the Quality of Life (QOL) and EORTC QOL-C30 questionnaires
Description
Number of participants having good outcome versus low outcomes. High score means worse health outcomes and low score means better health outcomes
Time Frame
10 years
Title
Protocol therapy interruption
Description
Number of participants that have protocol therapy interruption
Time Frame
10 years
Title
Discontinuation of protocol therapy
Description
Number of participants that have discontinuation of protocol therapy
Time Frame
10 years
Title
Rates of dose reduction of cyclophosphamide
Description
Number of participants that have dose reduction of cyclophosphamide
Time Frame
10 years
Title
Rates of dose reduction of methotrexate
Description
Number of participants that have dose reduction of methotrexate
Time Frame
10 years
Title
Rates of dose reduction of capecitabine
Description
Number of participants that have dose reduction of capecitabine
Time Frame
10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Abiola Ibreeheem, MD
Phone
312-413-1581
Email
abiolai@uic.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Prathmika Jha, BS
Phone
312-413-2746
Email
pjha7@uic.edu
Facility Information:
Facility Name
University of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abiola R Ibreeheem, MD
Phone
312-413-1581
Email
abiolai@uic.edu
First Name & Middle Initial & Last Name & Degree
Prathmika Jha, BS
Phone
312-413-2746
Email
pjha7@uic.edu

12. IPD Sharing Statement

Learn more about this trial

BRE-08 Phase II Study of CMC Regimen for Early Stage Breast Cancer

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