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

Sonya Reid

Status and phase

Enrolling

Phase 2

Conditions

Metastatic Breast Cancer

Invasive Mammary Carcinoma

Treatments

Other: Endocrine-therapy

Drug: Capecitabine

Other: MammoPrint ® and BluePrint assays

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05693766

VICCBRE2256

Details and patient eligibility

About

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)

Full 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

Enrollment

64 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.