Selinexor 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 24, 2019
|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. Secondary clinical study objectives
- - 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 with PFS on last prior anti-cancer therapy.
Translational Study Objective:1.- To explore the relationship between GIST genotype and CBR with selinexor and imatinib.
Pharmacokinetics Study Objective: 1.- To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Phase Ib/II, single-arm, non-randomized, open-label, multicenter, national clinical trial, combination products.|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Phase Ib/II Trial of Selinexor 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 in combination with imatinib
This is a single-arm, open label studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly. The study will consist of an initial escalation phase evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, TKI-refractory GIST patients.
oral selinexor given once weekly.
Other Name: Drug Combination
imatinib 400 mg, once daily
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.
- 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.
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: Beatriz Suarez, PhDfirstname.lastname@example.org|
|Contact: Melissa Fernandez, PMemail@example.com|
|Hospital Virgen del Rocio||Recruiting|
|Sevilla, Andalucia, Spain, 41013|
|Contact: Laura Bernal, SC 671 533 319 firstname.lastname@example.org|
|Principal Investigator: Javier Martín Broto, MD|
|H Vall d'Hebrón||Recruiting|
|Barcelona, Catalonia, Spain, 08035|
|Contact: Carlos Fernández Sáez, SC email@example.com|
|Principal Investigator: Cesar Serrano García, MD|
|Hospital Universitario de Canarias||Not yet recruiting|
|Tenerife, Islas Canarias, Spain, 238320|
|Contact: Rita Alonso, SC 922 678204 firstname.lastname@example.org|
|Principal Investigator: Josefina Cruz, MD|
|Hospital Miguel Servet||Not yet recruiting|
|Zaragoza, Zaragoza, Aragón, Spain, 50009|
|Contact: Laura Rodriguez, SC 976765500 ext 143825 email@example.com|
|Principal Investigator: Javier Martínez, MD|
|Hospital La Paz||Not yet recruiting|
|Madrid, Spain, 28046|
|Contact: Susana Feliu, SC 91 727 75 16 firstname.lastname@example.org|
|Principal Investigator: Virgina Martínez, MD|
|Hospital Virgen de la Arrixaca||Not yet recruiting|
|Murcia, Spain, 30120|
|Contact: Paula Ruiz, SC 968 36 93 87 email@example.com|
|Contact: Ana Perez, SC 968 36 93 87 firstname.lastname@example.org|
|Principal Investigator: Jerónimo Martínez, MD|
|Principal Investigator:||Cesar Serrano, MD||Hospital Vall d´Hebron|