PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• SULmax in relation to pCR [Срок оценки: 8 months]

Вторичные конечные точки (2)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

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

Публикации

• 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

Идентификаторы

NCT: NCT06245889 · J2395 · IRB00398141

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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