Status:
UNKNOWN
Selinexor as Single Agent and With Imatinib in Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (SeliGIST)
Lead Sponsor:
Grupo Espanol de Investigacion en Sarcomas
Conditions:
Maximum Tolerated Dose
GIST
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
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 o...
Detailed Description
Clinical Study Objectives: Primary clinical study objective Cohort A: 1.- To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of selinexor in combination with imatin...
Eligibility Criteria
Inclusion
- Age ≥18 years at the time of study entry.
- Histologically confirmed metastatic and/or unresectable GIST. Patients must demonstrate prior failure to at least imatinib. Any number of previous therapies for GIST is allowed.
- Failure of imatinib is defined as disease progression after ≥ 6 months of treatment with imatinib for advanced/metastatic disease. Exception to this rule is GIST patients with documented KIT or PDGFRA mutations.
- Measurable disease per modified RECIST 1.1.
- ECOG performance status 0 to 2.
- Adequate hematopoietic function (within 7 days prior to enrollment):
- Hemoglobin ≥ 9.0 g/dL (90 g/L).
- Absolute neutrophil count ≥ 1000/mm3.
- Platelets ≥ 100,000 /mm3. Patients must have at least a 2-week interval from the last red blood cell (RBC) transfusion and/or growth factor support prior to the Screening hemoglobin and neutrophil assessment. However, patients may receive RBC, growth factor support, and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
- Adequate organ function (within 7 days prior to enrollment):
- Alanine aminotransferanse (ALT) and aspartate aminotransferanse (AST)
- ≤2.5 x upper limit of normal (ULN), or ≤ 5.0 x ULN if liver metastases are present.
- Alkaline phosphatase (ALP) limit \< 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are present.
- Total serum bilirubin ≤ 2 x ULN. Patients with Gilbert's syndrome must have a total bilirubin of \< 3 × ULN.
- Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault
- Patients must be able to swallow oral medication and no malabsorption condition.
- Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug.
- Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion
- Cohort A: Intolerance to first-line treatment imatinib 400mg daily.
- Use of any approved tyrosine kinase inhibitors or investigational agents within 1 week or 5 half-lives of the agent, whichever is shorter, prior to receiving study drugs.
- Participants who have had radiotherapy within 4 weeks prior to study entry.
- Major surgery or significant traumatic injury within 4 weeks prior to study entry.
- Presence of symptomatic or uncontrolled brain or central nervous system metastases.
- Known or suspected allergy or hypersensitivity to the selinexor, imatinib or any of its components.
- Patient has a history of another primary malignancy that has been diagnosed or required therapy within 1 year prior to the first dose of study drug (The following are exempt from the 1-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.)
- Unstable cardiovascular function: • Symptomatic ischemia, or • Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or • Congestive heart failure (CHF) NYHA Class ≥ 3, or • Myocardial infarction (MI) within 3 months. • Left ventricular ejection fraction \< 40 %. • Hypertension \> 140 mm Hg systolic or \> 90 mm Hg diastolic with or without antihypertensive therapy.
- Ongoing infection \> Grade 2.
- Patients with any seizure disorder requiring medication.
- HIV-positive individuals on combination antiretroviral.
- Patients with active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
- Serious psychiatric or medical conditions that could interfere with treatment.
- Pregnant or lactating females.
- Strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole, ketoconazole , nefazodone , nelfinavir , posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) within 28 days or 5 drug half-lives (if drug half-life in patients is known), whichever is longer, before start of study treatment.
Key Trial Info
Start Date :
August 16 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 16 2023
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT04138381
Start Date
August 16 2019
End Date
April 16 2023
Last Update
March 27 2023
Active Locations (6)
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1
Hospital Virgen del Rocio
Seville, Andalusia, Spain, 41013
2
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Canary Islands, Spain, 238320
3
H Vall d'Hebrón
Barcelona, Catalonia, Spain, 08035
4
Hospital Miguel Servet
Zaragoza, Zaragoza, Aragón, Spain, 50009