Selinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT05035745|
Recruitment Status : Recruiting
First Posted : September 5, 2021
Last Update Posted : September 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Refractory Solid Tumors Advanced Triple Negative Breast Cancers Metastatic Triple Negative Breast Cancers||Drug: Talazoparib Drug: Selinexor||Phase 1 Phase 2|
Hypothesis The investigators hypothesize that the combination of Talazoparib and Selinexor will have clinical efficacy in TNBC, independent of BRCA mutation status.
- 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.
• To determine the objective response rate to combination Talazoparib and Selinexor in advanced/ metastatic TNBCs.
- 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|
|Estimated Enrollment :||63 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
Phase I Patients will be treated with Talazoparib daily and Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days) in a modified 3+3 dose escalation/ de-escalation design
Phase II 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 objective response analysis, TNBC patients will be stratified into platinum-naïve/platinum sensitive versus platinum-resistant to determine if prior platinum sensitivity impacts objective response rates to the combination of Talazoparib and Selinexor.
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose Finding Study of Selinexor and Talazoparib in Patients With Advanced Refractory Solid Tumors, Followed by Phase II Expansion Cohort Study in Patients With Advanced/ Metastatic Triple Negative Breast Cancers. (START)|
|Actual Study Start Date :||March 1, 2021|
|Estimated Primary Completion Date :||November 2024|
|Estimated Study Completion Date :||November 2025|
Experimental: Patients with refractory solid tumors
Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of patients with refractory solid tumors to determine the RP2D.
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)
- safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors using NCI CTCAE toxicity grading version 5.0. [ Time Frame: 5 years ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05035745
|Contact: Soo Chin Lee||6779 email@example.com|
|National University Hospital||Recruiting|
|Principal Investigator:||Soo Chin Lee||National University Hospital, Singapore|