PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

Purpose

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).

Condition

  • Triple Negative Breast Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
Female
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Sequential Assignment
Intervention Model Description
Eligible patients with stage 2 and 3 TNBC (ER<10% eligible) will be treated with 4 cycles of paclitaxel/carboplatin/pembrolizumab prior to surgery. 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 RD 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).
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Neoadjuvant therapy 		4 cycles of paclitaxel/carboplatin/pembrolizumab
  • Drug: Paclitaxel
    chemotherapy
    Other names:
    • Taxol
  • Drug: Carboplatin
    chemotherapy
    Other names:
    • Paraplatin
  • Drug: Pembrolizumab
    immunotherapy
    Other names:
    • Keytruda
  • Drug: Doxorubicin
    additional chemotherapy - neoadjuvant or adjuvant rescue
    Other names:
    • Adriamycin
  • Drug: Cyclophosphamide
    additional chemotherapy - adjuvant rescue
    Other names:
    • Cytoxan
  • Drug: Olaparib
    adjuvant rescue
    Other names:
    • Lynparza
  • Drug: Capecitabine
    adjuvant rescue
    Other names:
    • Xeloda

Recruiting Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland 21287
Contact:
Hopkins Breast Trials
410-614-1361
HopkinsBreastTrials@jhmi.edu

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland 21287
Contact:
JHCCCRO
410-955-8866
jhcccro@jhmi.edu

More Details

Status
Recruiting
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Contact

Cesar A Santa-Maria, MD
410-614-0874
csantam2@jhmi.edu

Detailed 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.