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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



Phase II

What is the purpose of this trial?

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.

  • Trial with
    Criterium, Inc.
  • Start Date
  • End Date

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