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Breast Diseases

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Palbociclib

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Adjuvant Therapy

Femi Okubanjo

Nick Alfonso

Alexia Demitsas, MS

Pavani Chalasani, MD, MPH

Grace Facio

Janice Lu, MD, PhD

Parisa Mirzadehgan

Reva Basho, MD

Leah Adams

Melissa Cross

Peter Kabos, MD

Adam Blanchard

Lajos Pusztai, MD

Ogochukwu Chukudi

Ashley Trumbull

Manali Bhave, MD

Michelle Loch, MD

Ellen R Wojcik

Ursa Brown-Glaberman, MD

Esther Kim

Paula Klein, MD

Alison Stopeck, MD

Pushpa Talanki

Christina Hayduchok

Sagar Sardesai, MD

Jennifer Fritts

Wajeeha Razaq, MD

Jeanette Phillips

Zahi Mitri, MD

Kim Reeves

Fenting Yan, MD

UW Cancer Connect

Amanda Parkes, MD

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

Surveillance population and ctDNA screening (up to 1000 patients): Clinically high risk, stage II-III, ER positive, HER2-, breast cancer patients who are currently receiving adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen are eligible for ctDNA screening if they meet any one of the following criteria for high risk for recurrence: (i) predicted risk of distant recurrence or death equal to or greater than 15% calculated by PREDICT, RSPC, or CTS5 (for late recurrence), (ii) four or more positive axillary lymph nodes or ipsilateral supraclavicular involvement regardless of tumor size, (iii) primary tumor equal to or greater than 5 centimeters regardless of nodal status, (iv) patients with 1-3 positive nodes, regardless of tumor size are eligible if at least one of the following is also true: grade 3 histology, greater than or equal to 3 cm tumor size, high molecular risk score (i.e. Oncotype Dx Recurrence score(RS) \> 26, MammaPrint high risk, EndoPredict \> 4, Prosigna score \> 60).

In order to start ctDNA surveillance, patients must be currently receiving endocrine therapy and have completed at least 6 months, but no more than 7 years and with at least 3 more years of planned 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. However, participants in the PENELOPE and PALLAS clinical trials are not eligible.

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. The investigators 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, the investigators allow starting ctDNA screening up to 7 years after starting adjuvant endocrine therapy if a patient meets criteria for high risk.

DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer

A Randomized Phase II Trial Of Circulating Tumor DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer

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 negative breast cancer who are receiving standard of care adjuvant endocrine therapy but remain high risk for recurrence.

Primary objective of the therapeutic randomized phase is to assess whether palbociclib plus fulvestrant improves relapse-free survival compared to standard of care adjuvant endocrine therapy in patients with ER+/HER2 negative breast cancer with detectable ctDNA in the plasma but without evidence of metastatic disease on imaging.

Estimate proportion of patients who have clinically apparent metastatic or local disease (i.e. imaging positive) at the time of first positive ctDNA result.

Assess the statistical correlation between ctDNA clearance, clinical relapse and the time to relapse in the control arm of the study.

Assess the statistical correlation between ctDNA clearance, relapse free survival and overall survival in the treatment arm of the study.

Compare the statistical correlation between ctDNA clearance, relapse free survival and overall survival in the two arms of the study.

To assess the tolerability and safety of treatments.

Criterium, Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer	NCT04567420	Breast Cancer	Palbociclib Fulvestrant Adjuvant Therap...	-	Criterium, Inc.
DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer	NCT04567420	Breast Cancer	Palbociclib Fulvestrant Adjuvant Therap...	-	Criterium, Inc.

Spots Global Cancer Trial Database for high residual risk