500 Participants Needed

Early Treatment Switch Strategies for Advanced Breast Cancer

Frances Valdes-Albini, MD profile photo
Overseen ByFrances Valdes-Albini, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: University of Miami
Must be taking: LHRH analogues
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had prior systemic anticancer therapy for metastatic or advanced disease, and you should not be on medications that are known to be cytochrome (CYP) 3A4 inhibitors or inducers within 7 days before starting the trial.

What safety data exists for CDK4/6 inhibitors in breast cancer treatment?

CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib, when combined with aromatase inhibitors or fulvestrant, have shown to be generally safe and effective in treating hormone receptor-positive, HER2-negative advanced breast cancer. However, they have different side effects, such as liver function test abnormalities and QTc prolongation (a heart rhythm issue) with ribociclib, which should be monitored. These treatments have been approved and are used in clinical practice, indicating a recognized safety profile.12345

What makes the Early Treatment Switch Strategies for Advanced Breast Cancer unique?

This treatment strategy is unique because it explores various combinations of drugs targeting different pathways, such as CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors, to overcome resistance in advanced hormone receptor-positive breast cancer. These combinations aim to improve progression-free survival and address resistance mechanisms that occur with standard endocrine therapies.34678

What evidence supports the effectiveness of the drug combination of AI+CDK4/6i for advanced breast cancer?

Research shows that combining CDK4/6 inhibitors with aromatase inhibitors (AI) significantly improves progression-free survival in hormone receptor-positive advanced breast cancer. Studies like MONARCH2 and PALOMA-1 have demonstrated that these combinations can also help overcome resistance to hormone treatments.347910

Who Is on the Research Team?

Dr. Frances Valdes, MD - Miami, FL ...

Frances Valdes-Albini, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for men and women over 18 with advanced breast cancer that can't be cured by surgery. They must have hormone receptor positive, HER2- metastatic breast cancer, no prior treatment for advanced disease, and their body should be functioning well enough to participate. Patients who've had certain other cancers or treatments recently aren't eligible.

Inclusion Criteria

My cancer has not spread to my organs in a way that threatens my life immediately.
I am fully active or restricted in physically strenuous activity but can do light work.
I am a woman who is postmenopausal, has suppressed ovarian function, or is premenopausal and willing to undergo hormone therapy for the trial.
See 9 more

Exclusion Criteria

I was treated with CDK4/6 inhibitors less than a year ago.
My breast cancer is advanced but can still be treated with the goal of curing it.
My electrolyte levels are stable and do not affect heart rhythm medications.
See 20 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Step 1: ctDNA Monitoring

Participants undergo ctDNA monitoring with blood samples collected at specified timepoints until a rise in ctDNA is detected.

Up to 36 months
Cycle 1 day 1, Day 30, Day 60, and every 8-9 weeks

Step 2: Treatment

Participants either continue current therapy or switch to an alternate therapy based on ctDNA results.

14 months

Step 3: Optional Treatment

Optional treatment for participants experiencing clinical progression, allowing a switch to alternative therapies.

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • AI+CDK4/6i
  • Chemotherapy
  • mTOR inhibitor + AI
  • mTOR inhibitor + Selective estrogen receptor modulator
  • mTOR inhibitor + SERD
  • PI3K inhibitor + AI
  • PI3K inhibitor + SERD
  • SERD+CDK4/6i
Trial Overview The study tests if switching breast cancer treatments when a blood marker (ctDNA) indicates the disease is progressing—before it's visible on scans—helps control the cancer longer. It compares early switchers to those who change treatments later based on standard methods like imaging results.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Step 3: Treatment for Patients in Arm 2Experimental Treatment1 Intervention
Group II: Step 3: Treatment for Patients in Arm 1Experimental Treatment11 Interventions
Group III: Step 2 Arm 2: Early Switch in TherapyExperimental Treatment11 Interventions
Group IV: Step 2 Arm 1: No Modification of TherapyExperimental Treatment2 Interventions

AI+CDK4/6i is already approved in United States, European Union for the following indications:

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Approved in United States as AI + CDK4/6i for:
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Approved in European Union as AI + CDK4/6i for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials
976
Recruited
423,000+

Published Research Related to This Trial

The PI3K/AKT/mTOR pathway is frequently activated in estrogen receptor-positive (ER+) breast cancer, making it a key target for new therapies, including the recently approved alpelisib and capivasertib, which are used in combination with fulvestrant for advanced cases.
The development of multiple inhibitors targeting this pathway, alongside CDK4/6 inhibitors, presents a complex landscape for personalizing treatment strategies in ER+ advanced breast cancer, necessitating careful consideration of genomic contexts for optimal efficacy.
Drugging the PI3K/AKT/mTOR Pathway in ER+ Breast Cancer.Alves, CL., Ditzel, HJ.[2023]
Data from multiple clinical trials (MONARCH2, PALOMA-1, and TREnd) indicate that combining CDK4/6 inhibitors with standard endocrine therapy significantly improves progression-free survival in patients with advanced ER-positive breast cancer.
The use of CDK4/6 inhibitors may also help to overcome acquired resistance to hormone treatments, enhancing the overall effectiveness of the therapy.
Treating ER+ Breast Cancer with CDK4/6 Inhibitors.[2021]
Oral CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib significantly improve progression-free survival by 40-45% when combined with endocrine therapy in hormone-responsive HER2-negative advanced breast cancer, particularly in post-menopausal women.
These inhibitors have varying toxicity profiles and monitoring requirements, and ongoing clinical trials are exploring their use in other breast cancer subtypes and in combination with other therapies to overcome resistance.
The Role of CDK4/6 Inhibitors in Breast Cancer.Murphy, CG.[2020]

Citations

Drugging the PI3K/AKT/mTOR Pathway in ER+ Breast Cancer. [2023]
Treating ER+ Breast Cancer with CDK4/6 Inhibitors. [2021]
The Role of CDK4/6 Inhibitors in Breast Cancer. [2020]
Enhancing Endocrine Therapy Combination Strategies for the Treatment of Postmenopausal HR+/HER2- Advanced Breast Cancer. [2018]
Cotargeting of CYP-19 (aromatase) and emerging, pivotal signalling pathways in metastatic breast cancer. [2018]
Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models. [2023]
Ribociclib in the Treatment of Hormone-Receptor Positive/HER2-Negative Advanced and Early Breast Cancer: Overview of Clinical Data and Patients Selection. [2022]
First clinical experience with CDK4/6 inhibitors in breast cancer therapy. [2021]
Practical Treatment Strategies and Future Directions After Progression While Receiving CDK4/6 Inhibition and Endocrine Therapy in Advanced HR+/HER2- Breast Cancer. [2021]
The PI3K/AKT/mTOR and CDK4/6 Pathways in Endocrine Resistant HR+/HER2- Metastatic Breast Cancer: Biological Mechanisms and New Treatments. [2023]
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