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 |
|
|
|
Experimental Capecitabine_Non-Luminal A subtypes |
|
Recruiting Locations
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Sonya Reid
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