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

Official title

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

Overview

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)

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

Interventions

• Drug Capecitabine
  2000 mg taken by mouth twice daily for 7 days on, 7 days off
• Other Endocrine-therapy
  Endocrine therapy administered
• Other MammoPrint ® and BluePrint assays
  Archival tissue will be analyzed using the MammoPrint ® and BluePrint assays

Primary outcome measures

• Progression free survival [Time frame: Up to 3 years]

Secondary outcome measures (7)

• Overall survival at 2 years [Time frame: Up to 2 years]
• Overall survival at 5 years [Time frame: Up to 5 years]
• Overall survival at 10 years [Time frame: Up to 10 years]
• Clinical Benefit Rate [Time frame: Approximately 6 months]
• Overall response rate [Time frame: Up to 3 years]
• Incidence of adverse events [Time frame: Up to 28 days post-treatment]
• Overall impact of treatment toxicity [Time frame: Up to 3 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• University of Alabama Birmingham — Birmingham
• Vanderbilt University/Ingram Cancer Center — Nashville
• UT Southwestern Medical Center — Dallas

Identifiers

NCT: NCT05693766 · VICCBRE2256

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗