Gastrointestinal stromal tumors. Gastrointestinal stromal tumors (GISTs) start their development in special cells in the wall of the gastrointestinal (GI) tract, also known as the digestive tract.
Conditions
Interventions
Trade Name: Pletal
Product Name: Pletal
Pharmaceutical Form: Tablet
INN or Proposed INN: CILOSTAZOL
CAS Number: 73963-72-1
Current Sponsor code: 201-476-4
Concentration unit: mg milligram(s)
Concentra
Sponsors
CUB HOPITAL ERASME
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: -histologically proven metastatic or locally advanced histologically proven non resectable GIST ( any primary tumor site) already treated by Glivec® (at any dose) for at least 12 months in first line therapy, or patients who will start Glivec® (at any dose) in first line therapy or after failure of all TKIs -exon 11, exon 9 or other kit mutations -written signed informed consent -ability to take oral medication -metabolic positivity of the tumor at the first PET-CT (positivity is defined as High 18F-FDG uptake by a lesion more than the surrounding tissue) -at least one measurable lesion by CT scanner -no contraindication to cilostazol -ECOG performance status 0 /1 at study entry -effective contraception for both male and female patients must be used for at least 8 weeks after the last study drug administration if the risk of conception exists -age > 18 years old -life expectancy at least 12 weeks - Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment: o Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: Exclusion Criteria: -PDGFR&D842V mutation -Wild-type tumors -unability to take oral medication -any malabsorption condition -previous exposure to cilostazol or PDE3 inhibitor or any other phosphodiesterase inhibitor -known hypersensitivity to any of the components of study treatments -previous malignancy in the last past 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix -pregnancy or breast feeding -medical or psychological conditions that would not permit the patient to complete the study or sign inform consent -patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study - history of organ allograft -ongoing infection HIV infection -liver failure, cirrhosis Child Pugh B or C -active chronic hepatitis B or C with a need for antiviral treatment -heart failure any NYHA class -grapefruit juice consumption -hemodialysis -active bleeding disorder or coagulation disorder -uncontrolled concurrent CNS, cardiac, infectious diseases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: -Evaluation of metabolic response on 18F-FDG PET using EORTC (PET Study Group) Criteria after 28 days of cilostazol treatment added to Glivec® Image will be analysed by 2 independants nuclear specialists Results will be statistically analysed by using the Wilcoxon rank test for paired observations. -Tolerability and safety of the combination therapy (evaluated using EORTC criteria, CTCAE version 4.0 for toxicity) ;Main Objective: The aims of this study are to confirm pre-clinical data and to evaluate the potential synergism between Glivec® and cilostazol in patient with unresectable or metastatic GIST of any primary (except PDGFR&D842V mutants), and also to evaluate the tolerability and safety of the combined therapy. Primary objective: Evaluation of metabolic response on 18F-FDG PET using EORTC (PET Study Group) Criteria after 28 days of cilostazol treatment added to Glivec® Image will be analysed by 2 independant nuclear specialists Results will be statistically analysed by using the Wilcoxon rank test for paired observations. Tolerability and safety of the combination therapy ;Secondary Objective: Evaluation of morphological response on thoraco-abdominal CT Scan using the radiological Choi Criteria based on the modifications of the size and/or tumor density (Hounsfeild Unit) of the lesions. Search of possible predictive factor of therapeutic response using statistical analysis by the Cox multivariate regression method ;Primary end point(s): -Evaluation of metabolic response on 18F-FDG PET using EORTC (PET Study Group) Criteria after 28 days of cilostazol treatment added to Glivec® Image will be analysed by 2 independants nuclear specialists Results will be statistically analysed by using the Wilcoxon rank test for paired observations. -Tolerability and safety of the combination therapy (evaluated using EORTC criteria, CTCAE version 4.0 for toxicity) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Evaluation of morphological response on thoraco-abdominal CT Scan using the radiological Choi Criteria based on the modifications of the size and/or tumor density (Hounsfeild Unit) of the lesions. -Search of possible predictive factor of therapeutic response using statistical analysis by the Cox multivariate regression method ;Timepoint(s) of evaluation of this end point: PET-CT scan at 28days under combination therapy imatinib (Glivec) and cilostazol (Pletal) started at day 56. | — |
Countries
Belgium
Contacts
Public ContactDEMOLS Anne
CUB HOPITAL ERASME
Outcome results
None listed