Evaluating chemotherapy versus endocrine therapy for hormone receptor-positive metastatic breast cancer

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

Phase 2 Interventional Vanderbilt-Ingram Cancer Center · NCT05693766

This study is testing whether a chemotherapy drug called capecitabine works better than hormone therapy for people with hormone receptor-positive metastatic breast cancer who have already tried other treatments.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment64 (estimated)
Ages18 Years and up
SexAll
SponsorVanderbilt-Ingram Cancer Center Academic / other
Drugs / interventionschemotherapy, radiation
Locations3 sites (Birmingham, Alabama and 2 other locations)
Trial IDNCT05693766 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter Phase II clinical trial aims to assess the effectiveness of second-line chemotherapy using capecitabine compared to an endocrine therapy-based regimen in patients with non-Luminal A hormone receptor-positive metastatic breast cancer. The primary objective is to determine the anti-tumor effects of these two treatment approaches. Additionally, the study will evaluate the safety and tolerability of capecitabine and explore the potential of tumor mutations in cfDNA as early indicators of treatment response and resistance. The trial will involve patients who have previously been treated with specific hormone therapies.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with stage IV invasive mammary carcinoma that is hormone receptor-positive and HER2 negative, who have previously been treated with specific hormone therapies.

Not a fit: Patients with Luminal A subtype breast cancer or those who have not been previously treated with aromatase inhibitors or SERMs may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with non-Luminal A hormone receptor-positive metastatic breast cancer.

How similar studies have performed: Other studies have shown promising results with similar approaches in treating metastatic breast cancer, indicating that this methodology is not entirely novel but builds on existing knowledge.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Birmingham, Alabama and 2 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Invasive Mammary CarcinomaMetastatic Breast Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.