Panitumumab and Pembrolizumab in Combination With Neoadjuvant Chemotherapy for the Treatment of Stage III-IV Triple Negative Breast Cancer

Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial

Official title: Enhancing Immunotherapy by Targeting the EGFR Pathway in Inflammatory Breast Cancer: A Phase II Study of Panitumumab (PmAb) and Pembrolizumab (Pembro) in Combination With Neoadjuvant Chemotherapy (NAC) in Patients With Newly Diagnosed Triple Negative Inflammatory Breast Cancer (TN-IBC)

Status Withdrawn

Clinical Trial Summary

This phase II trial tests whether panitumumab and pembrolizumab in combination with standard of care chemotherapy before surgery (neoadjuvant) works to shrink tumors in patients with stage III-IV triple negative breast cancer. Panitumumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab and pembrolizumab in combination with neoadjuvant chemotherapy may kill more tumor cells in patients with triple negative breast cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the pathological complete response (pCR rate) of the proposed combination in patients with newly diagnosed triple-negative inflammatory breast cancer (TN-IBC).

SECONDARY OBJECTIVES I. To evaluate the surgical complication rate after the completion of the proposed treatment.

II. To determine the change of EGR1 related to the efficacy of proposed treatment. (Key Secondary Objective) III. To determine the immunological change of tumor microenvironment (TME) related to the efficacy of proposed treatment. (Key Secondary Objective) IV. To define the cutoff or threshold of changes of EGR1, which will correlate with the pCR.

V. To define the cutoff or threshold of immunological changes of TME, which will correlate with the pCR.

VI. To determine two-year recurrence-free survival (RFS) rates. VII. To determine two-year overall survival (OS) rates. VIII. To determine the safety and tolerability. IX. To determine the predictive biomarkers to predict the therapeutic response. (correlative study)

OUTLINE:

CYCLES 1-4: Patients receive pembrolizumab intravenously (IV) over 30 minutes and panitumumab IV over 30-60 minutes on day 1 of cycle 0. Cycle 0 continues for 7 days in the absence of disease progression or unacceptable toxicity. Patients then receive panitumumab IV over 30-60 minutes on days 1, 8, and 15 of cycles 1-3 and days 1 and 8 of cycle 4, pembrolizumab IV over 30 minutes on day 1 of cycles 2-4, paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1, 8 and 15 of cycles 1-4. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

CYCLES 5-8: Patients receive standard of care treatment, including pembrolizumab IV over 30 minutes, doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 90 days, then every 6 months for 2 years from date of surgery. ;

Related Conditions & MeSH terms

• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IIIA Breast Cancer AJCC v8
• Anatomic Stage IIIB Breast Cancer AJCC v8
• Anatomic Stage IIIC Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Breast Inflammatory Carcinoma
• Breast Neoplasms
• Carcinoma
• Invasive Breast Carcinoma
• Prognostic Stage III Breast Cancer AJCC v8
• Prognostic Stage IIIA Breast Cancer AJCC v8
• Prognostic Stage IIIB Breast Cancer AJCC v8
• Prognostic Stage IIIC Breast Cancer AJCC v8
• Prognostic Stage IV Breast Cancer AJCC v8
• Triple-Negative Breast Carcinoma

• NCT number: NCT05177796
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Withdrawn
• Phase: Phase 2
• Start date: March 11, 2022
• Completion date: July 26, 2023