Active clinical trials for "Triple Negative Breast Neoplasms"

Recent evidences suggest that zoledronate, one of the most used bisphosphonates (BPs) in the clinical setting for the prevention and treatment of bone metastasis in cancer patients, may have antitumor activity in early breast cancer. The ABCSG-12 clinical trial have reported improved Disease Free Survival (DFS) and Overall Survival (OS) in mostly chemotherapy naive premenopausal patients after a 3-years of treatment with zoledronate (zol) and ovarian-suppression therapy. The ZO-FAST study showed better DFS for immediate use of zol in postmenopausal patients receiving adjuvant hormonal treatment. Preliminary evidences support the role of zoledronate also in neoadjuvant setting reporting better responses in cases of treatment with zol and chemotherapy (cht) compared with cht alone. The anticancer mechanism of action of BPs still remains not well understood. Basically, BPs are mevalonate (MVA) pathway inhibitors and one of the most intriguing hypothesis supporting their anticancer activity relies on the modulation of the mevalonate downstream metabolism. Selected cancer subtypes may present a more pronounced mevalonate activity able to confer an aggressive phenotype. It has been shown that a mutant p53 acts as promoter of MVA upregulation. One of the most important biological implications of MVA pathway upregulation in cancer cells is the aberrant activation of the Hippo pathway, a molecular axis with a central role in carcinogenesis. Two Hippo pathway related transcriptional coactivators, YAP and TAZ, promote tissue proliferation and the self-renewal of normal and cancer stem cells, and incite metastasis. Due to the strong interplay between the MVA and Hippo pathways, the modulation of MVA axis has deep impact on the function of YAP/TAZ as transcriptional regulators of tumour growth. These findings implicate the mevalonate pathway as a therapeutic target for selected tumors with up-regulation of these pathways. Preclinical and clinical evidences suggest that BPs are able to interfere with YAP/TAZ expression, via MVA pathway. This kind of activity may be part of the mechanism of action of BPs as antitumor drugs. Others medications are able to modulate the MVA pathway. Statins, a first-class of lipid-lowering medications that inhibit the enzyme HMG-CoA reductase, inhibit the sterol biosynthesis via the mevalonate pathway. A possible anti-tumor effect of statins can be predicted with the same mechanism of action described for BPs, through the interference with the MVA axis. Actually, the anti-tumor activity of statins have been investigated in different retrospective analyses. In breast cancer a more robust signal has been retrospectively reported and prospective studies have enquired the exquisite antitumor activity of statins in pre-operative breast cancer setting. From above, the clinical trial herein proposed aims to investigate the antitumoral clinical activity of zoledronate (zol) and statins (atorvastatin) combination, in patients receiving neoadjuvant chemotherapy for triple-negative breast cancer (TNBC). The primary objective of the study is to address in patients with TNBC the antitumor activity of pre-operative standard chemotherapy associated or not with zoledronate (zol) and atorvastatin measured through its effect on YAP and TAZ immunochemistry (IHC) expressions, which are considered co-primary objectives. The primary clinical objective is to assess the anti-tumor activity of the combination of neoadjuvant standard cht associated with zol and atorvastatin, measured by the proportion of pCR obtained after neoadjuvant treatment in patients with TNBC. Secondary objectives are: 1) to evaluate the anti-tumor activity of pre-operative standard chemotherapy associated or not with zol and atorvastatin according to high/low p53 levels 2) to address the efficacy of neoadjuvant cht associated or not with zol/atorvastatin combo in terms of disease free survival and overall survival); 3) to study the safety profile of study treatments; 4) to investigate the treatment modulation of YAP and TAZ gene expression (RNA-Seq) in tumor tissues collected at the time of core-biopsy and definitive surgery; 5) to address the modulation of Ki67expression by IHC in the FFPE diagnostic core biopsy tumor block and in the tumor tissue collected at surgery. Patients fulfilling the eligibility criteria will be randomized to receive standard anthracyclines/taxanes based neoadjuvant cht (ARM A) or the combination of zol and atorvastatin associated with the above mentioned neoadjuvant cht (ARM B).

Triple-negative breast cancer (TNBC) is a heterogeneous disease that is associated with a younger age of onset, worse stage matched-outcomes, and women of African ancestry in North America. A higher incidence of TNBC is also seen in West Africa, despite unique environmental, socioeconomic and modifiable risk factors. Transcriptome analysis of TNBC has delineated four distinct subgroups with therapeutic and prognostic significance. With further characterization, important regional differences have emerged between populations of African vs. European ancestry. These differences may have significant implications for the efficacy of novel TNBC-targeted therapy and need to be further evaluated. Transcriptional data on TNBC in sub-Saharan African also offers the opportunity to evaluate the relationship between breast cancer phenotype and ancestry-linked differences in the tumor-immune microenvironment.

The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician's choice (TPC) as measured by independently-reviewed Independent Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) previously treated with at least two systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and without brain metastasis at baseline.

A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients with Advanced Solid Tumors

The purpose of this study is to evaluate the safety, tolerability and clinical activity of pembrolizumab (MK-3475) in combination with six chemotherapy regimens as neoadjuvant treatment for participants with triple negative breast cancer (TNBC).

This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC). Part 1 of the study will examine the efficacy and safety of pembrolizumab monotherapy as first line or above treatment in participants who have received either no prior systemic treatment or at least one prior systemic treatment for metastatic breast cancer. Part 2 of the study, if done, will expand the investigation of pembrolizumab treatment in a subgroup of participants from Part 1 and will only start after enrollment in Part 1 has been completed. There will be no hypothesis testing in this study.

The main purpose of this study is to see whether the combination of selinexor (KPT-330) can help people with triple negative breast cancer (TNBC). Researchers also want to study the safety and tolerability of Selinexor in TNBC patients.

This is a 3 arm Phase 3 study to evaluate the safety and efficacy of the addition of veliparib plus carboplatin versus the addition of carboplatin to standard neoadjuvant chemotherapy versus standard neoadjuvant chemotherapy in subjects with early stage TNBC.

This phase II trial studies how well trametinib and v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor GSK2141795 work in treating patients with triple-negative breast cancer (breast cancer cells that do not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 [HER2/neu] protein) that has spread to other places in the body. Trametinib and Akt inhibitor GSK2141795 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

This is a phase II study randomizing patients with stage I with T1 > 1.5 cm, stage II or III triple negative breast cancer (TNBC) to preoperative cisplatin versus paclitaxel. The study is designed to evaluate the ability of the Homologous Recombination Deficiency (HRD) assay to predict pathologic response to preoperative chemotherapy.