Selinexor as a Single Agent and in Combination With Imatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors. (SeliGIST)
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|ClinicalTrials.gov Identifier: NCT04138381|
Recruitment Status : Recruiting
First Posted : October 24, 2019
Last Update Posted : October 23, 2020
This is a single-arm, two cohort, open label phase I/II clinical trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of:
- Cohort A: an initial escalation phase (Ib) evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, imatinib-resistant GIST patients, followed by an expansion phase (II) testing for safety and preliminary evidence of antitumor activity
- Cohort B: single-agent, fixed selinexor dose in the same target population
|Condition or disease||Intervention/treatment||Phase|
|Maximum Tolerated Dose GIST Metastatic Adult Soft Tissue Sarcoma Drug Toxicity Drug Use||Drug: Selinexor Drug: Imatinib||Phase 1 Phase 2|
Clinical Study Objectives:
Primary clinical study objective
1.- To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of selinexor in combination with imatinib among unresectable and/or metastatic GIST patients with prior failure to at least imatinib for advanced/metastatic disease.
1. To evaluate the clinical benefit rate (CBR: CR+PR+SD ≥ 16 wks)
Secondary clinical study objectives (both cohorts A and B)
- To evaluate the clinical benefit rate (CBR: CR+PR+ SD ≥ 16 wks)
- To evaluate progression free survival (PFS)
- To evaluate overall survival (OS)
- To evaluate the objective response rate (ORR)
- To evaluate the safety profile according to CTCAE 4.03
- To compare PFS on selinexor and imatinib and on selinexor in monotherapy with PFS on last prior anti-cancer therapy.
Translational Study Objective - To explore the relationship between GIST genotype and CBR with selinexor and imatinib, and selinexor as single-agent
Pharmacokinetics Study Objective
- To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Phase Ib/II, single-arm, two-cohort, non-randomized, open-label, multicenter, national clinical trial, single agent, combinations products|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Phase Ib/II Trial of Selinexor as a Single Agent and in Combination With Imatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GISTs)|
|Actual Study Start Date :||August 16, 2019|
|Estimated Primary Completion Date :||April 16, 2022|
|Estimated Study Completion Date :||December 1, 2022|
selinexor as a single agent and in combination with imatinib
This is a single-arm, two-cohort, open label phase Ib/II trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of:
oral selinexor given once weekly (Cohort A), oral selinexor given BIW (Cohort B)
imatinib 400 mg, once daily (Cohort A)
Other Name: Drug Combination
- Maximum tolerated dose (MTD) for the use of Imatinib in combination with Selinexor [ Time Frame: 32 months ]Maximum tolerated dose (MTD) is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT) during the first 28 days of treatment. Dose escalation cohort (Phase 1b) seeks to determine the frequency and characteristics of DLTs of the selinexor plus imatinib combination at each dose level during the first cycle of therapy. Phase Ib will be carried out in standard 3+3 format, based on the toxicities found during the first cycle of therapy.
- Clinical benefit rate (CBR) for the use of selinexor in monotherapy [ Time Frame: 24 months ]Clinical benefit rate (CBR) is defined as CR+PR+SD ≥ 16 wks
- Progression free survival (PFS) [ Time Frame: 32 months ]Efficacy measured by PFS assessed by median time. PFS is defined as the time between the date of first experimental treatment dose and the date of disease progression (according to RECIST 1.1 criteria).
- Overall survival (OS) [ Time Frame: 32 months ]Efficacy measured by OS. OS is defined as the time between the date of first experimental treatment dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive, or when the last enrolled patiens are followed up to for 12 months, whichever is early.
- Objective response rate (ORR) [ Time Frame: 32 months ]Efficacy measured by ORR. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 and Choi criteria).
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 32 months ]
Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Toxicity will be graded and tabulated by using CTCAE 4.03.
- GIST genotype and CBR with selinexor and imatinib (Translational) Study Objective [ Time Frame: 32 months ]GIST genotype determinations and its correlation with response to the treatment with selinexor and imatinib in terms of clinical benefit (CBR).
- Measure the plasma concentration of imatinib and selinexor (Pharmacokinetics)Study Objective [ Time Frame: 32 months ]To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.
- Clinical benefit rate (CBR) [ Time Frame: 24 months ]Number of patient with CBR ≥ 30% lasting ≥ 16 weeks
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): NCT04138381
|Contact: Martina Giuppi, MScfirstname.lastname@example.org|
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|Sevilla, Andalucia, Spain, 41013|
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|Principal Investigator: Javier Martín Broto, MD|
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|Barcelona, Catalonia, Spain, 08035|
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|Zaragoza, Zaragoza, Aragón, Spain, 50009|
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|Murcia, Spain, 30120|
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