PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

Official title

A Pilot Study of Neoadjuvant Response-Adapted Chemotherapy With Pembrolizumab in Patients With Stage 2 and 3 Triple Negative Breast Cancer to Determine Early PET and Biomarker Dynamics

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).

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.

Interventions

• Drug Paclitaxel
  chemotherapy
• Drug Carboplatin
  chemotherapy
• Drug Pembrolizumab
  immunotherapy
• Drug Doxorubicin
  additional chemotherapy - neoadjuvant or adjuvant rescue
• Drug Cyclophosphamide
  additional chemotherapy - adjuvant rescue
• Drug Olaparib
  adjuvant rescue
• Drug Capecitabine
  adjuvant rescue

Primary outcome measures

• SULmax in relation to pCR [Time frame: 8 months]

Secondary outcome measures (2)

• Pathologic complete response (pCR) [Time frame: 3 years]
• Circulating tumor deoxyribonucleic acid (ctDNA) clearance [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Stage II-III TNBC - estrogen receptor (ER) and progesterone receptor (PR) up to and including 10% is eligible
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Eligible for standard chemo-immunotherapy as determined by treating physician, including consideration of:

• Adequate marrow and organ function
• Co-morbid conditions do not preclude the use of chemo-immunotherapy (such as uncontrolled autoimmune disease, or the use of immunosuppressive medications)
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore

Publications

• Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549. PMID 32101663
• Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative br PMID 32966830

Identifiers

NCT: NCT06245889 · J2395 · IRB00398141

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗