DNA-Guided Adjuvant Therapy for Breast Cancer

(DARE Trial)

Recruiting in Palo Alto (17 mi)

+13 other locations

Overseen by Lajos Pusztai, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Criterium, Inc.

Must be taking: Aromatase inhibitors, Tamoxifen

Must not be taking: Fulvestrant, CDK4/6 inhibitors

Disqualifiers: Invasive cancer, HER2 positive, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

A randomized, Phase II trial of circulating tumor DNA-guided second line Adjuvant therapy for high Residual risk, Estrogen Receptor positive, HER-2 negative breast cancer (DARE)

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it does allow patients who are currently taking an aromatase inhibitor or tamoxifen as adjuvant endocrine therapy. However, you cannot be on a CDK4/6 inhibitor or certain other medications that interact with trial drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Fulvestrant and Palbociclib for breast cancer?

Research shows that the combination of Palbociclib and Fulvestrant improves progression-free survival (PFS) in women with advanced estrogen receptor-positive breast cancer. Early changes in circulating tumor DNA (ctDNA) levels can predict how well patients respond to this drug combination. ^{1 2 3 4 5}

Is DNA-guided adjuvant therapy for breast cancer safe?

The combination of palbociclib (Ibrance) and fulvestrant (Faslodex) has been approved for treating certain types of advanced breast cancer and is generally well-tolerated. Common side effects include low white blood cell counts, infections, tiredness, nausea, and anemia, but these are manageable in most cases. ^{1 4 6 7 8}

How is DNA-Guided Adjuvant Therapy for Breast Cancer different from other treatments?

This treatment is unique because it uses DNA markers to guide therapy decisions, potentially allowing for more personalized treatment plans based on the genetic profile of the tumor, unlike standard treatments that do not typically use such specific genetic information. ^{1 2 4 5 9}

Research Team

Lajos Pusztai, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for men and women with stage II-III, HER2 negative, ER positive breast cancer who have been on hormone therapy for 6 months to 7 years. They must not show signs of cancer spread and agree to use contraception. Those with high recurrence risk or ctDNA positivity are eligible. Exclusions include intolerance to the drugs being tested, severe health issues, living outside the US, certain cancer histories, or taking specific medications.

Inclusion Criteria

My breast cancer is stage II or III, HER2 negative, and ER positive.

My scans show no cancer spread to other parts of my body.

I agree to use birth control during and after the trial if I am a woman who can still have children or a man.

Exclusion Criteria

I haven't had cancer in the last 5 years, except for skin cancer.

I am on medication that strongly affects liver enzyme levels and cannot switch.

I have been treated with fulvestrant, a CDK4/6 inhibitor, or was in the PENELOPE/PALLAS trials.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 7 years

Routine follow-up clinic visits every 4 to 6 months

Surveillance/ctDNA Screening

Assess the incidence of ctDNA detection in patients with ER positive HER2- breast cancer receiving standard of care adjuvant endocrine therapy

Enrollment period

Treatment

Randomized patients receive either palbociclib plus fulvestrant or continue standard of care endocrine therapy

Up to 2 years

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Fulvestrant (Estrogen Receptor Antagonist)
• Palbociclib (CDK4/6 Inhibitor)

Trial Overview The DARE trial tests if adding Palbociclib and Fulvestrant (second line adjuvant therapies) can benefit patients with a high residual risk of breast cancer after initial treatment. It's randomized: some will get standard care while others receive the new combination; decisions are made by chance.

Participant Groups

Group I: Arm A Experimental Treatment 2 Interventions

Palbociclib/Fulvestrant Combination

Group II: Arm B Active Control 1 Intervention

Adjuvant Therapy

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

New Mexico Cancer Care Alliance Albuquerque, NM

Icahn School of Medicine at Mount Sinai New York, NY

Stony Brook University Cancer Center Stony Brook, NY

Louisiana State University Health Sciences Center- New Orleans New Orleans, LA

More Trial Locations

Who Is Running the Clinical Trial?

Criterium, Inc.

Lead Sponsor

Trials

18

Patients Recruited

730+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer. O'Leary, B., Cutts, RJ., Huang, X., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients. Pascual, J., Gil-Gil, M., Proszek, P., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of response to CDK4/6 inhibitors in the real-world setting. Witkiewicz, AK., Schultz, E., Wang, J., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients. Darrigues, L., Pierga, JY., Bernard-Tessier, A., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. O'Leary, B., Hrebien, S., Morden, JP., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. Mycock, K., Zhan, L., Hart, K., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer. Iwamoto, T., Niikura, N., Watanabe, K., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Determinants of response to CDK4/6 inhibitors in the real-world setting. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer. [2023]