RNA Disruption Assay (RDA)-Breast Cancer Response Evaluation for Individualized Therapy BREVITY

Official Title

RNA Disruption Assay (RDA)-Breast Cancer Response Evaluation for Individualized Therapy (BREVITY)

Summary:

The current study (BREVITY) aims to provide validation results of RNA Disruption Assay (RDA) as a tumour response assessment tool that uses tumour core biopsies at ~2-3 weeks after the initiation of neoadjuvant chemotherapy.

Trial Description

Primary Outcome:

  • Pathological complete response (pCR)
Secondary Outcome:
  • Disease-free survival
Study Rationale: There is some evidence that identifying non-responders early in neoadjuvant treatment and offering alternative agents (response-guided therapy) increased pathological complete response (pCR) rates and/or survival resulting in improved care and incremental cost effectiveness. Differentiating non-responders to chemotherapy from responders with reliable guidance tools early during therapy is crucial to the success of response-guided therapy. The current study (BREVITY) aims to provide validation results of RDA as a tumour response assessment tool that uses tumour core biopsies at
  • 2-3 weeks after the initiation of neoadjuvant chemotherapy. Study Objectives and Endpoints: The primary objective of the BREVITY study is to determine the 2 RDI cut-offs to have a diagnostic test optimized in terms of both negative and positive predictive values NPV and PPV (in a training set of patients i.e. phase 1 of the study) for predicting nopCR/pCR and to establish the performance characteristics for the first cut-off (test result "zone 1") in terms of NPV as primary endpoint (in a validation set i.e. phase 2). The secondary objective is to assess the test's NPV in the different cancer subtypes and the test's PPV in Her2+ patients; also to assess and compare pCR prevalence and DFS (secondary endpoint) in zones 1-3 for all patients and each cancer subtype. Patient Population: The study aims to enrol approximately 725 patients. Approximately 270 patients will be enrolled in 17 German centres, 100 patients in 5 centres in the US, 100 patients in 4-5 centres in Canada, 125 patients in 10 centres in Italy and 130 patients in 6 centres in further European countries (Austria, France, Scotland, Belgium, Ireland). The population consists of patients diagnosed with invasive breast cancer and scheduled to receive neoadjuvant chemotherapy as part of standard of care treatment. Throughout the study, patients will receive standard of care neoadjuvant chemotherapy treatments including taxanes, anthracyclines or other targeted drugs and drug combinations as prescribed based on the investigators' / clinicians' choice. Adjuvant therapies (e.g. radiation therapy, hormonal treatment … etc.) may be prescribed to patients according to standard of care and independently of the RDI score results. RDA is presently in an experimental stage and clinicians will not receive or use the RDA results in this study. Biopsy Collection, Storage and Shipment:
    • 1st core needle biopsy for RDA 2 specimens: Time Point:
  • 2-3 weeks after initiation of 1st cycle of chemotherapy; Timing by type of drug schedule 3-weekly: at 16 days +/- 2 days, Bi-weekly: at day of 2nd dose preferably before drug admin., Weekly: at day of 4th dose preferably before drug admin.
    • 2nd core needle biopsy for RDA: Time Point: if therapy is changed (as part of SoC), a second biopsy
  • 2-3 weeks after initiation of new drugs; Timing by type of drug schedule 3-weekly: at 16 days +/- 2 days, Bi-weekly: at day of 2nd dose preferably before drug admin., Weekly: at day of 4th dose preferably before drug admin. Statistical Plan: The study consists of a training set / phase 1 (114 fully evaluable patients) to determine response zone cut-offs using pCR outcomes and RDA's predictive values, and a validation set / phase 2 (500 fully evaluable patients) to validate the performance characteristics of the RDA test. The study aims to enrol 725 patients in order to achieve an accrual of 614 fully evaluable patients which is the number required to adequately statistically power the trial. Combined statistical analysis and various subgroup analyses will be performed for the primary and secondary objectives. Duration and Follow-up: There will be an 18 months of active patient accrual (or until last patient is accrued) in addition to 60 months of patient follow-up.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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