This is a single arm, open-label, phase I dose finding study, followed by a phase II expansion study. Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of 33 patients with refractory solid tumors to determine the RP2D. In the phase II portion, a total of 30 patients with advanced/metastatic TNBC will be enrolled.
Hypothesis The investigators hypothesize that the combination of Talazoparib and Selinexor will have clinical efficacy in TNBC, independent of BRCA mutation status. Primary Objectives * To determine the safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors. * To determine the RP2D of Talazoparib and Selinexor combination therapy in patients with advanced/ metastatic solid tumors. Secondary Objectives • To determine the objective response rate to combination Talazoparib and Selinexor in advanced/ metastatic TNBCs. Exploratory Objectives * To assess the effect of the combination on pharmacokinetics of Talazoparib and Selinexor * To explore the impact of pharmacogenetics on toxicity and efficacy of combination Talazoparib and Selinexor. * To assess changes in circulating tumor cells and plasma biomarkers during treatment. * To assess pharmacodynamic changes and predictive biomarkers in tumor tissue during treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Patients will be treated with Talazoparib daily on a 4 weekly cycle (28 days)
Patients will be treated with Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days)
National University Hospital
Singapore, Singapore
RECRUITINGsafety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors using NCI CTCAE toxicity grading version 5.0.
Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final Safety evaluations will be performed for all patients prior to each cycle of treatment, and include taking a medical history, physical examination, adverse event documentation, full blood count, renal function, liver function tests and electrocardiogram (ECG). Toxicities will be graded using the NCI CTCAE toxicity grading version 5.0.
Time frame: 5 years
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