DNA-guided Second Line Adjuvant Therapy for High Residual Risk, Estrogen Receptor Positive, HER-2 Negative Breast Cancer (DARE)
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT04567420
- Lead Sponsor
- Criterium, Inc.
- Brief Summary
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)
- Detailed Description
Surveillance population and ctDNA screening (up to 1000 patients): High risk ER positive, HER2-, breast cancer patients who have completed adjuvant endocrine therapy, or are currently receiving adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen and are within 7 years since completion of definitive breast surgery are eligible for ctDNA screening.
In order to start ctDNA surveillance, patients must have completed at least 6 months, but no more than 7 years of adjuvant endocrine therapy of treatment without distant recurrence. Prior adjuvant CDK4/6 therapy is allowed, but at least 12 months must have elapsed since completing CDK4/6 therapy and enrolling into ctDNA surveillance on this study. Participants in the PENELOPE and PALLAS clinical trials who received Palbociclib are also eligible if meet all required eligibility criteria.
For screening, patients will undergo Signatera testing during routine follow up clinic visits. The current ASCO/NCCN breast cancer practice guidelines recommend follow up visits every 4 to 6 months at the treating physician's discretion. We anticipate that screening positivity rates will be the highest in patients between years 1-5 after initial diagnosis, based on the annual hazard rates of recurrence in ER positive breast cancer.
However, since up to 50% of all recurrences occur after 5 years of follow-up, we allow starting ctDNA screening up to 7 years after starting adjuvant endocrine therapy if a patient meets criteria for high risk.
Randomized phase II (N=100): Patients who become ctDNA positive during ctDNA surveillance will have systemic staging with CT of the chest, abdomen and pelvis, and those without radiographic evidence of metastatic disease will be randomized 1:1 to receive palbociclib plus fulvestrant for two years or continue standard of care endocrine therapy. Pre- and peri- menopausal patients randomized to the fulvestrant palbociclib arm will require GnRH analogue therapy. Patients in both treatment arms may continue adjuvant bisphosphonate therapy and patients in the control arm may switch between different brands of aromatase inhibitors for better tolerance or patient preference. No other, non-protocol directed anticancer therapy is allowed. The maximum duration of treatment is 2 years. A patient may complete a maximum of 26 cycles of treatment (for patients without interruptions or delays). The goal is not to administer a specific number of cycles, but to allow for the completion of any cycles initiated prior to 2 years from randomization. Patients who have completed 2 years of fulvestrant and palbociclib without recurrence may resume their originally planned standard of care adjuvant therapy to complete a total of 5 or 10 years of endocrine therapy at the discretion of the treating physician.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 70
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B Adjuvant Therapy Adjuvant Therapy Arm A Palbociclib Palbociclib/Fulvestrant Combination Arm A Fulvestrant Palbociclib/Fulvestrant Combination
- Primary Outcome Measures
Name Time Method Surveillance/ctDNA screening Phase enrollment Primary objective of the ctDNA screening (surveillance) phase is to assess the incidence of ctDNA detection (i.e. ctDNA positivity) in patients with ER positive HER2- breast cancer who are receiving standard of care adjuvant endocrine therapy but remain high risk for recurrence.
Therapeutic Phase through study completion, an average of 6 years Primary objective of the therapeutic randomized phase is to assess whether palbociclib plus fulvestrant improves relapse free survival compared to standard endocrine therapy in patients with ER positive HER2 negative breast cancer with detectable circulating tumor DNA during adjuvant endocrine therapy without clinical evidence of metastatic disease.
- Secondary Outcome Measures
Name Time Method Secondary Objective 1: Feasibility- correlation between clinically apparent metastatic or local disease and positive ctDNA result. enrollment Estimate proportion of patients who have clinically apparent metastatic or local disease (i.e. imaging positive) at the time of first positive ctDNA result.
Secondary Objective 2: Efficacy- assess the ability of positive ctDNA results to predict clinical relapse. through study completion, an average of 6 years Assess the positive predictive value and specificity of positive ctDNA result to predict subsequent clinical relapse, and estimate the time to relapse in the control arm of the randomized trial.
Secondary Objective 3: Efficacy- assess whether ctDNA clearance is associated with improved relapse free survival and overall survival. through study completion, an average of 6 years To assess whether ctDNA clearance is associated with improved relapse free survival and overall survival compared to non-clearance in the palbociclib plus fulvestrant arm.
Secondary Objective 4: Efficacy- assess the efficacy of the combination arm, palbociclib plus fulvestrant compared to the control arm. through study completion, an average of 6 years To assess whether palbociclib plus fulvestrant compared to the control arm improves (i) ctDNA clearance at 3, 6 and 24 months, (ii) distant metastasis free survival, (iii) invasive disease-free survival, (iv) overall survival, (v) the number of patients who are recurrence free at 24 months.
Secondary Objective 5: Safety and Tolerability- number of participants with treatment-related adverse event as assed by CTCAE V5.0. through study completion, an average of 6 years To assess the tolerability and safety of treatments.
Trial Locations
- Locations (15)
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
The Ohio State University Wexner Medical Center James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Wisconsin Clinical Science Center
🇺🇸Madison, Wisconsin, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Louisiana State University Health Sciences Center- New Orleans
🇺🇸New Orleans, Louisiana, United States
New Mexico Cancer Care Alliance
🇺🇸Albuquerque, New Mexico, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Stony Brook University Cancer Center
🇺🇸Stony Brook, New York, United States