DNA-Guided Adjuvant Therapy for Breast Cancer
(DARE Trial)
Recruiting in Palo Alto (17 mi)
+13 other locations
Overseen byLajos 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.
12345Is 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.
14678How 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.
12459Eligibility 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.
+6 more
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.
+8 more
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm AExperimental Treatment2 Interventions
Palbociclib/Fulvestrant Combination
Group II: Arm BActive Control1 Intervention
Adjuvant Therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
New Mexico Cancer Care AllianceAlbuquerque, NM
Icahn School of Medicine at Mount SinaiNew York, NY
Stony Brook University Cancer CenterStony Brook, NY
Louisiana State University Health Sciences Center- New OrleansNew Orleans, LA
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Criterium, Inc.Lead Sponsor
References
Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer. [2023]There are no established molecular biomarkers for patients with breast cancer receiving combination endocrine and CDK4/6 inhibitor (CDK4/6i). We aimed to determine whether genomic markers in circulating tumor DNA (ctDNA) can identify patients at higher risk of early progression on fulvestrant therapy with or without palbociclib, a CDK4/6i.
Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients. [2023]Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy.
Determinants of response to CDK4/6 inhibitors in the real-world setting. [2023]Despite widespread use and a known mechanism of action for CDK4/6 inhibitors in combination with endocrine therapy, features of disease evolution and determinants of therapeutic response in the real-world setting remain unclear. Here, a cohort of patients treated with standard-of-care combination regimens was utilized to explore features of disease and determinants of progression-free survival (PFS) and overall survival (OS). In this cohort of 280 patients, >90% of patients were treated with palbociclib in combination with either an aromatase inhibitor (AI) or fulvestrant (FUL). Most of these patients had modified Scarff-Bloom-Richardson (SBR) scores, and ER, HER2, and PR immunohistochemistry. Both the SBR score and lack of PR expression were associated with shorter PFS in patients treated with AI combinations and remained significant in multivariate analyses (HR = 3.86, p = 0.008). Gene expression analyses indicated substantial changes in cell cycle and estrogen receptor signaling during the course of treatment. Furthermore, gene expression-based subtyping indicated that predominant subtypes changed with treatment and progression. The luminal B, HER2, and basal subtypes exhibited shorter PFS in CDK4/6 inhibitor combinations when assessed in the pretreatment biopsies; however, they were not associated with OS. Using unbiased approaches, cell cycle-associated gene sets were strongly associated with shorter PFS in pretreatment biopsies irrespective of endocrine therapy. Estrogen receptor signaling gene sets were associated with longer PFS particularly in the AI-treated cohort. Together, these data suggest that there are distinct pathological and biological features of HR+/HER2- breast cancer associated with response to CDK4/6 inhibitors. Clinical trial registration number: NCT04526587.
Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients. [2022]Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency.
Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. [2022]CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.
Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. [2022]Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates. Neutropenia was the most commonly reported any-grade and grade ≥ 3 adverse event. It was infrequently associated with febrile neutropenia (
Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. [2022]Aim: To report the Europe Ibrance Real World Insights study findings. Methods: Physicians abstracted demographic/clinical characteristics, treatment and outcomes data for women with HR+/HER2- locally advanced breast cancer (ABC) or metastatic  breast cancer (MBC) receiving palbociclib + aromatase inhibitor (AI) or palbociclib + fulvestrant. Kaplan-Meier analysis estimated progression-free rates (PFRs) and survival rates (SRs). Results: 238 physicians abstracted data for 1723 patients. For patients (>90%) initiating at 125 mg/day, dose was reduced in 18.9% of palbociclib + AI and 12.3% of palbociclib + fulvestrant patients. At 12 months, PFR for palbociclib + AI was 88.1%, and SR was 97.3%; PFR for palbociclib + fulvestrant was 79.8%, and SR was 97.5%. Conclusion: Low dose-reduction rates and favorable PFRs and SRs suggest that palbociclib + AI/fulvestrant is well tolerated and effective for HR+/HER2- ABC/MBC in real-world clinical practice.
FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). The primary endpoint was investigator-assessed progression-free survival (PFS). A statistically significant and clinically meaningful improvement in PFS (9.5 months vs. 4.6 months) was observed in patients receiving palbociclib plus fulvestrant [HR 0.46; 95% confidence interval (CI), 0.36-0.59; P 20%) in patients treated with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, and thrombocytopenia. This approval was granted in the context of a prior accelerated approval for palbociclib in combination with letrozole in patients with HR-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. Clin Cancer Res; 22(20); 4968-72. ©2016 AACR.
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]Here, we investigated the potential predictive and elucidating efficacy of cell-free DNA (cfDNA) changes on clinical outcomes and biological effects, respectively, after short-term palbociclib and fulvestrant treatment for patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer (ABC).