Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer

Summary

The majority of patients (pts) with breast cancer have hormone receptor positive (HR+) disease, and this holds true for pts with advanced breast cancer (ABC). Currently frontline therapy for pts with HR+ ABC is antihormonal therapy with an aromatase inhibitor or selective estrogen receptor degrader plus a CDK4/6i. The proposed trial is a randomized study to further evaluate the potential benefit of switching a frontline regimen at the time that a molecular signal, ctDNA, suggests progression prior to detection of clinical progression using standard methods. The purpose of this study is to determine whether switching treatment earlier in the disease process, based on molecular progression, will increase the amount of time that a patient's metastatic breast cancer is controlled compared to patients with metastatic breast cancer who receive treatment later based on diagnostic imaging results or other methods currently used in medical practice.

Conditions

• Breast Cancer
• ER-positive Breast Cancer
• HER2-negative Breast Cancer
• Metastatic Breast Cancer

Interventions

DRUG

AI+CDK4/6i

Participants will receive standard of care one of three available AI therapies in combination with one of three available CDK4/6i therapies: * AI: Anastrozole, Letrozole or Exemestane * CDK4/6i: Palbociclib, Ribociclib or Abemaciclib

DRUG

SERD+CDK4/6i

Participants will receive standard of care SERD therapy in the form of Fulvestrant, in combination with one of three one of three available CDK4/6i therapies: * SERD: Fulvestrant * CDK4/6i: Palbociclib, Ribociclib or Abemaciclib

DRUG

mTOR inhibitor + AI

Participants will receive standard of care mTOR inhibitor therapy (Everolimus) in combination with AI therapy (Exemestane) in Step 2 Arm 2 and Step 3. mTOR inhibitor + AI therapy administered as one of the available options for early switch from AI+CDK4/6i or SERD+CDk4/6i therapy in administered in Step 1.

DRUG

mTOR inhibitor + SERD

Participants will receive standard of care mTOR inhibitor therapy (Everolimus) in combination with SERD therapy (Fulvestrant), in Step 2 Arm 2 and Step 3. mTOR inhibitor + SERD therapy administered as one of the available options for early switch from AI+CDK4/6i or SERD+CDk4/6i therapy in administered in Step 1.

DRUG

mTOR inhibitor + Selective estrogen receptor modulator

Participants will receive standard of care mTOR inhibitor therapy (Everolimus) in combination with selective estrogen receptor modulator therapy (Tamoxifen) in Step 2 Arm 2 and Step 3. mTOR inhibitor + Selective estrogen receptor modulator therapy administered as one of the available options for early switch from AI+CDK4/6i or SERD+CDk4/6i therapy in administered in Step 1.

DRUG

PI3K inhibitor + SERD

Participants will receive standard of care one PI3K inhibitor therapy (Alpelisib), in combination with SERD therapy (Fulvestrant) in Step 2 Arm 2 and Step 3. PI3K inhibitor + SERD therapy administered as one of the available options for early switch from AI+CDK4/6i or SERD+CDk4/6i therapy in administered in Step 1.

DRUG

PI3K inhibitor + AI

Participants will receive standard of care a PI3K inhibitor therapy (Alpelisib), in combination with an AI therapy (Letrozole) in Step 2 Arm 2 and Step 3. PI3K inhibitor + AI therapy administered as one of the available options for early switch from SERD+CDk4/6i therapy in administered in Step 1.

DRUG

Chemotherapy

Chemotherapy administered standard of care as an alternative therapy in Step 2 Arm 2 and Step 3.

DRUG

Oral SERD

Participants will receive standard of care oral SERD therapy (Elacestrant) in Step 2 Arm 2 and Step 3. Oral SERD therapy administered as one of the available options for early switch from AI+CDK4/6i or SERD+CDk4/6i therapy in administered in Step 1.

DRUG

PARPi

For participants with germline breast cancer gene (BRCA) mutation(s). Participants will receive standard of care PARPi (Olaparib or Talazoparib) therapy in Step 2 and Step 3.

DRUG

AKT inhibitor

For participants with tumors with one or more phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) or AKT serine/threonine kinase 1 (AKT1) or phosphatase and tensin homolog (PTEN) alterations. Participants in Step 2 and Step 3 will receive standard of care AKT inhibitor as an alternative therapy.

OTHER

Step 3 Arm 2

Participants will receive third-line treatment standard of care as per their treating physician's choice according to National Comprehensive Cancer Network (NCCN) guidelines.

Sponsors & Collaborators

• University of Miami

  lead OTHER

Principal Investigators

• Frances Valdes-Albini, MD · University of Miami

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-12

Primary Completion

2026-07-31

Completion

2029-07-31

FDA Drug

Yes

Countries

• United States

Study Locations