NCT05826964

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

Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer: A Phase 2 Randomized, Open-Label Study

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: University of Miami · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Type	Name	Description
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.

Timeline

• Start date: 2023-06-12
• Primary completion: 2026-07-31
• Completion: 2029-07-31
• First posted: 2023-04-24
• Last updated: 2026-01-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study