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

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

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)

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; Invasive Mammary Carcinoma
• Intervention / Treatment: Other: Endocrine-therapy; Other: MammoPrint ® and BluePrint assays; Drug: Capecitabine

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

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vanderbilt-Ingram Services for Timely Access; Phone Number: 800-811-8480; Email: cip@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University/Ingram Cancer Center
      • Principal Investigator: Sonya Reid, MD
      • Contact: Vanderbilt-Ingram Service for Timely Access; Phone Number: 800-811-8480; Email: cip@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Other: MammoPrint ® and BluePrint assays; Archival tissue will be analyzed using the MammoPrint ® and BluePrint assays; Drug: Capecitabine; 2000 mg taken by mouth twice daily for 7 days on, 7 days off

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival at 2 years		Up to 2 years
Overall survival at 5 years		Up to 5 years
Overall survival at 10 years		Up to 10 years
Clinical Benefit Rate	Percentage of patients without disease progression at 6 months	Approximately 6 months
Overall response rate		Up to 3 years
Incidence of adverse events		Up to 28 days post-treatment
Overall impact of treatment toxicity	Will be measured using Functional Assessment of Cancer Therapy (FACT)-G (5 point Likert-type scale from 1 ("none at all") to 5 ("very much")	Up to 3 years

Collaborators and Investigators

• Sponsor: Sonya Reid
• Collaborators: Susan G. Komen Breast Cancer Foundation; Agendia
• Investigators: Principal Investigator: Sonya Reid, MD, Vanderbilt University/Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2037

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: VICCBRE2256

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No