BRE-10: Biomarker Optimization of Neoadjuvant Therapy in Breast Cancer

Breast Cancer Clinical Trial

— BRE-10  

Official title:

BRE-10: BIomarker OptimizatioN of NeOadjuVAnt Therapy in BrEast Cancer: The INNOVATE Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06441890
• Other study ID #: 2023-1384
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: June 2028

Study information

• Verified date: June 2024
• Source: University of Illinois at Chicago
• Contact: kent hoskins
• Phone: 3123550496
• Email: khoski[@]uic.ed
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Adult men and women with early-stage, IHC/FISH-defined HER2-positive breast cancer will have a MammaPrint®/BluePrint® assay performed on the diagnostic biopsy specimen, ordered by the treating Oncologist as standard care

Description:

Adult men and women with early-stage, IHC/FISH-defined HER2-positive breast cancer will have a MammaPrint®/BluePrint® assay performed on the diagnostic biopsy specimen, ordered by the treating Oncologist as standard care. Patients whose tumors have a HER2-enriched molecular subtype on the MammaPrint®/BluePrint® assay and are recommended for neoadjuvant chemotherapy by their treating Oncologist will be recruited for study enrollment

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: June 2028
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 core needle or surgical biopsy with 90 days prior to study registration.

• HER2-positive by IHC or FISH according to ASCO/CAP 2018 guidelines

• HER2-enriched subtype on the MammaPrint/BluePrint gene expression profile within 90 days prior to study registration.

• Curative resection of primary breast tumor(s) is planned; ipsilateral axillary nodes will be sampled by sentinel lymph node biopsy or axillary dissection

• Treating Oncologist recommends neoadjuvant chemotherapy

• No evidence of distant metastatic disease

• AJCC clinical stage: cT1c-T3, cN0-N2

• Baseline left ventricular ejection fraction (LVEF) of at least 50% on Echo or MUGA scan within 90 days prior to registration.

Adequate organ function as defined below:

Leukocytes =2,000/mm3 Platelet count = 75,000/mm3 Absolute Neutrophil Count (ANC) = 1,000/mm3 Hemoglobin (Hgb) = 9.0 g/dL Creatinine/Calculated Creatine clearance (CrCI) Cr < 1.5 x upper limit of normal (ULN) or CrCl = 50 mL/min using the Cockcroft-Gault formula 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

• Patients with synchronous bilateral primary breast tumors or multiple ipsilateral primary breast tumors are eligible if the treating Oncologist determines that the assigned treatment 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, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization. or the Legally Authorized Representative (LAR) is able to provide consent and HIPAA authorization.

• Women of childbearing potential must agree to use a barrier form of contraception if they are sexually active with a male partner 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.

• Patients with history of HIV/AIDS (acquired immunodeficiency syndrome) are eligible for this study if they are receiving anti-retroviral therapy and it does not include any medications known to alter metabolism or tolerability of component drugs in the protocol treatment regimen and the following criteria is met:

• Patients without a history of AIDS-defining opportunistic infections within the past 12 months.

• Patients with Hepatitis B (HBV): chronic carriers of HBV infection (HBsAg-positive) or individuals who have serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and anti-HBc-positive) are eligible if they are receiving appropriate suppressive antiviral therapy that does not include medications known to alter metabolism or tolerability of component drugs in the protocol treatment (see Appendix) prior to initiation of cancer therapy, and liver function tests meet study eligibility criteria.

• Patients with Hepatitis C (HCV): patients with a history of HCV infection who have completed curative antiviral treatment are eligible if the HCV RNA viral load is below the limit of quantification within 90 days of study enrollment. Patients on concurrent HCV treatment must have HCV RNA viral load below the limit of quantification within 30 days of study enrollment. Patients must also meet liver function test eligibility requirements and antiviral therapy does not include medications known to alter metabolism or tolerability of component drugs in the protocol treatment

Exclusion Criteria

• Any prior therapy for this breast cancer

• Active infection requiring systemic therapy at the time of study registration

• Pregnant or nursing

• 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., compromised liver function, major cardiovascular or cerebrovascular event within the past 6 months, uncontrolled diabetes mellitus or hypertension), as determined by treating physician.

• Any contraindication for any chemotherapy drug used in the assigned regimen.

• Baseline sensory neuropathy > grade 1

• History of hypersensitivity to any of the drugs in the treatment regimen. Patients with history of hypersensitivity may be treated on this protocol with either nab-paclitaxel or docetaxel.

• Prisoners

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

Drug:
• Paclitaxel
80mg/m2 IV D1, 8, 15
• Nab-paclitaxel
125mg/m2 IV D1, 8, 15
• Docetaxel
75mg/m2 IV D1
• Trastuzumab
8mg/kg loading, then 6mg/kg IV/SQ D1
• Pertuzumab
840 mg loading, then 420mg IV/SQ D1

Locations

Country	Name	City	State
United States	University of Illinois	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants that have a pathological complete response (pCR)	This is defined as the absence of any residual invasive carcinomancer on hematoxylin and eosin evaluation of the resected breast specimen and any resected lymph node tissue	16 weeks
Secondary	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	Baseline
Secondary	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	30 days post treatment
Secondary	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	6 months post treatment
Secondary	Safety of the study treatment with be assessed by evaluating the number of participants experiencing Adverse Events (AEs)	AEs will be evaluated using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5	30 days post treatment
Secondary	Treatment tolerability will be assessed	Number of participants that have cycle treatment delays	30 days post treatment
Secondary	Treatment tolerability will be assessed	Number of participants that have cycle treatment cancelations	30 days post treatment
Secondary	Treatment tolerability will be assessed	Number of participants that have dose reductions	30 days post treatment