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

Metastatic Breast Cancer Clinical Trial

— INSIGHT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05693766
• Other study ID #: VICCBRE2256
• Status: Recruiting
• Phase: Phase 2
• Start date: September 11, 2023
• Est. completion date: August 31, 2037

Study information

• Verified date: April 2024
• Source: Vanderbilt-Ingram Cancer Center
• Contact: Vanderbilt-Ingram Services for Timely Access
• Phone: 800-811-8480
• Email: cip[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: August 31, 2037
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Invasive Mammary Carcinoma
• Metastatic Breast Cancer

Intervention

Drug:
• Capecitabine
2000 mg taken by mouth twice daily for 7 days on, 7 days off

Other:
• Endocrine-therapy
Endocrine therapy administered
• MammoPrint ® and BluePrint assays
Archival tissue will be analyzed using the MammoPrint ® and BluePrint assays

Locations

Country	Name	City	State
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
Sonya Reid	Agendia, Susan G. Komen Breast Cancer Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		Up to 3 years
Secondary	Overall survival at 2 years		Up to 2 years
Secondary	Overall survival at 5 years		Up to 5 years
Secondary	Overall survival at 10 years		Up to 10 years
Secondary	Clinical Benefit Rate	Percentage of patients without disease progression at 6 months	Approximately 6 months
Secondary	Overall response rate		Up to 3 years
Secondary	Incidence of adverse events		Up to 28 days post-treatment
Secondary	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