Vanderbilt Clinical Trials

Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort

Purpose

This is an open-label, multicenter, two-arm Phase II clinical trial that will evaluate the impact of 2nd line chemotherapy (i.e. capecitabine) on survival in patients with non-Luminal A hormone receptor-positive (HR+) metastatic breast cancer (MBC)

Conditions

Invasive Mammary Carcinoma
Metastatic Breast Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Signed and dated written informed consent. - Subjects ≥ 18 years of age. - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. - Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is: - ER (>/=1%) and/or PR (>/= 1%) by IHC and HER2 negative (by IHC or FISH) - Previously exposed to an aromatase inhibitor (AI) or a selective estrogenreceptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor. - Prior radiation permitted (if completed at least 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity (≤ grade 1) induced by this treatment (except for alopecia) - Patients with brain metastasis secondary to breast cancer and clinically stable for more than 4 weeks from completion of radiation treatment and off steroids - Evaluable disease (measurable or non-measurable) - Measurable disease, ie, at least 1 measurable lesion as per RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) - Patients with bone only disease allowed if possible to evaluate on radiological exams (eg.bone scan, PET/CT, CT, MRI) even if lesions are non-measurable according to RECIST1.1. - Adequate organ function including: - Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L - Platelets ≥ 100 × 10^9/L - Hemoglobin ≥ 8/g/dL (may have been transfused) - Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN) - Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present) - Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50mL/min as calculated using the Cockcroft-Gault (CG) equation - For randomized patients only: tumors must be diagnosed as non-Luminal A using the Blueprint® and Mammaprint® tests

Exclusion Criteria

Prior chemotherapy in the metastatic setting - Previous malignant disease other than breast cancer within the last 2 years with associated competing risk, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment). - Persisting symptoms related to prior therapy that has not reduced to Grade 1 [National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0]; however, menopausal symptoms, alopecia, and sensory neuropathy Grade ≤ 2 is acceptable - Pregnant or breastfeeding females.

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Active Comparator Physician's Choice of Endocrine-based Therapy_Non-Luminal A subtypes		Other: Endocrine-therapy Endocrine therapy administered Other: MammoPrint ® and BluePrint assays Archival tissue will be analyzed using the MammoPrint ® and BluePrint assays
Experimental Capecitabine_Non-Luminal A subtypes		Drug: Capecitabine 2000 mg taken by mouth twice daily for 7 days on, 7 days off Other: MammoPrint ® and BluePrint assays Archival tissue will be analyzed using the MammoPrint ® and BluePrint assays

Recruiting Locations

Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232

Contact:
Vanderbilt-Ingram Service for Timely Access
800-811-8480
cip@vumc.org

More Details

Status: Recruiting
Sponsor: Sonya Reid

Study Contact

Vanderbilt-Ingram Services for Timely Access
800-811-8480
cip@vumc.org

Detailed Description

Primary Objective: - Determine the impact of early chemotherapy (i.e., capecitabine) versus endocrine therapy-based regimen on anti-tumor effect in patients with non-Luminal A hormone receptor-positive (HR+) metastatic breast cancer Secondary Objectives: - Compare the safety and tolerability of capecitabine versus endocrine therapy in patients with non-Luminal A hormone receptor-positive (HR+) metastatic breast cancer - Determine the impact of early chemotherapy (i.e., capecitabine) versus endocrine therapy-based regimen on anti-tumor effect in patients with non-Luminal A hormone receptor-positive (HR+) metastatic breast cancer Correlatives: - Determine if the tumor mutations detected in cfDNA are early surrogates of response - Determine if the cfDNA results at disease progression show new genomic alterations potentially associated with resistance to therapy

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.