Pembrolizumab and Carboplatin in Treating Patients With Circulating Tumor Cells Positive Metastatic Breast Cancer
brief summary
The purpose of the study is to evaluate the impact on progression-free survival (PFS) with the combination carboplatin - pembrolizumab in patients with CTC (circulating tumor cells) positive, HER2 negative metastatic breast cancer previously treated with anthracyclines and taxanes. Previous studies have indicated that recurrent breast cancers are more resistant to chemotherapy and maybe associated with a weak immune system. This study is investigating the use of an immune therapy drug, pembrolizumab, that has the ability to restore the capacity of controlling and killing cancer cells of an important component of your immune system called T-cells. Pembrolizumab has been found effective in other types of cancer and has already been approved by FDA for those indications, but the efficacy in breast cancer is still unknown. In this study, pembrolizumab will be combined with chemotherapy to increase the cancer cell killing. There is no control or placebo treatment in this study.
detailed description
PRIMARY OBJECTIVES:
I. Evaluate the impact on progression free survival (PFS) of the combination pembrolizumab - carboplatin in patients with circulating tumor cells (CTC) positive, HER2 negative metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes in primary setting.
SECONDARY OBJECTIVES:
I. Evaluate the impact on overall survival (OS) of the combination carboplatin - pembrolizumab in patients with CTC positive MBC previously treated with anthracyclines and taxanes in primary setting.
II. To assess the overall response rate or objective response rate (ORR) and clinical benefit rate (CBR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with carboplatin - pembrolizumab in patients with CTC positive MBC previously treated with anthracyclines and taxanes in primary setting.
III. To assess immune-related response using tumor response by immune-related RECIST (irRECIST) as immune-related partial response (irPR) or immune-related complete response (irCR).
IV. Measure the time to new metastases (TTNM). V. Evaluate ORR and clinical benefit in relation to PDL-1 expression in tissue and CTCs.
TERTIARY OBJECTIVES:
I. Measure immune biomarkers (PDL-1) in CTCs (CellSearch) and immune cells such as cancer-associated macrophage-like cells (CAMLs) (CellSieve) and correlate with therapeutic benefit.
II. Measure cell-free circulating tumor deoxyribonecleic acid (ctDNA) and T-cell receptor sequencing analysis and correlate them with CTC enumeration and therapeutic benefit.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and carboplatin IV over 30-60 minutes on day 1 beginning with course 3. Courses repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, every 9 weeks for 1 year, and then every 12 weeks.
official title
I-CURE-1: A Phase II, Single Arm Study of Pembroluzimab Combined With Carboplatin in Patients With Circulating Tumor Cells (CTCs) Positive Her-2 Negative Metastatic Breast Cancer (MBC)