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PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

Recruiting
18 years and older
Female
Phase 2

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Overview

Eligible patients with stage 2 and 3 triple negative breast cancer will be treated with 4 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab. A PET scan will be performed at baseline and after 1 cycle of therapy. A breast MRI will be performed after treatment completion. Patients with complete clinical response will proceed to surgery. Patients with clinical residual disease will complete neoadjuvant rescue with 4 cycles of doxorubicin/cyclophosphamide prior to surgery. If residual disease identified after surgery, adjuvant therapy to be determined by the treating oncologist (may include doxorubicin/cyclophosphamide/pembrolizumab, capecitabine etc).

Description

Eligible participants will undergo baseline procedures including research bloodwork, MRI and PET scan. Participants will then be treated with one cycle of paclitaxel, carboplatin and pembrolizumab (TCarbo/pembro). At the end of Cycle one patients will undergo repeat procedures (bloodwork and PET scan), and then continue with treatment for an additional three cycles. ctDNA will be collected on day 1 of each cycle. At the end of treatment patients will undergo repeat MRI.

Patients achieving a clinical complete response (CR) on MRI will proceed with surgery. Patients with clinical residual disease (RD) on MRI will be recommended a biopsy, and be recommended "rescue" neoadjuvant doxorubicin and cyclophosphamide with pembrolizumab (AC/pembro) for four additional cycles, and then proceed with surgery. Note: patients/treating physician may opt to proceed with surgery.

Archival tissue will be collected from the surgical product. Patients achieving a pathologic CR (pCR) may proceed with adjuvant pembrolizumab per standard of care, and treating physician's discretion. Patients with pathological RD may proceed with "rescue" adjuvant AC/pembrolizumab for four additional cycles (if not given neoadjuvantly), per treating physician discretion. The participants may also receive Aadjuvant capecitabine or olaparib as indicated and per treating physician's discretion.

Eligibility

Inclusion Criteria:

  1. Stage II-III TNBC - estrogen receptor (ER) and progesterone receptor (PR) up to and including 10% is eligible
  2. Age ≥ 18 years
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  4. Eligible for standard chemo-immunotherapy as determined by treating physician, including consideration of:
    1. Adequate marrow and organ function
    2. Co-morbid conditions do not preclude the use of chemo-immunotherapy (such as uncontrolled autoimmune disease, or the use of immunosuppressive medications)
  5. Patients must have the ability to understand and the willingness to sign a written

    informed consent prior to registration on study

Exclusion Criteria:

  1. Patients unable to undergo PET or MRI
  2. Evidence of metastatic disease or loco-regional recurrence (i.e. distant or chest wall recurrence)
  3. Inflammatory breast cancer
  4. Previous treatment with paclitaxel, carboplatin, or immune checkpoint inhibitors

Study details
    Triple Negative Breast Cancer

NCT06245889

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

14 May 2024

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