patients with unresectable and/or metastatic gastrointestinal stromal tumours with exon 18 PDGFRA mutation MedDRA version: 12.1 Level: LLT Classification code 10051066 Term: Gastrointestinal stromal tumour
Conditions
Interventions
Trade Name: GLIVEC
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: IMATINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Trade Name: CERTICAN
Phar
Sponsors
ISTITUTO NAZIONALE PER LA CURA TUMORI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age > 18 years. - Histological confirmed diagnosis of GIST with positive immunostaining for KIT (CD117) - Exon 18 PDGFRA-D842V mutation confirmed - Locally advanced disease and/or metastatic disease - Measurable or evaluable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter = 20 mm on conventional CT scan; = 10 mm on spiral CT) - WHO Performance Status 0, 1 or 2 - Patients must have normal organ, electrolyte, and marrow function as defined below: o Absolute Neutrophil Count (ANC) = 1.5x 109/L, o Platelets = 100 x 109/L, o Hemoglobin = 10g/dL (or Hematocrit > 29%). Blood transfusions are allowed to reach the baseline requested Hb level o Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Patients receiving chemotherapy, immunotherapy, radiation therapy or any other investigational agent within 4 weeks of the first dose of study drug. Previous treatment with imatinib in monotherapy is allowed. No previous treatment with any mTOR inhibitor is allowed. No use of other investigational cancer therapies during the study is allowed. - Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, known HIV infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function. - Uncontrolled diabetes (fasting glucose > 2 x ULN). - Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors (see Appendix 1). - Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone = 20 mg for adrenal insufficiency). Patients receiving corticosteroids must be on a stable dose for = 4 weeks prior to the first dose of everolimus. Topical or inhaled corticosteroids are permitted. - Patients with known history of hypersensitivity against imatinib or everolimus (or other rapamycin analogs), or to their excipients. - Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs. - Use of therapeutic coumarin derivatives (i.e. warfarin, acenoucumarol, phenprocoumon) - A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits - Patients unwilling or unable to comply with the protocol. - Patients with a history of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer - Patients presenting with known or symptomatic CNS metastases or leptomeningeal involvement
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to evaluate activity and safety of combination of imatinib to everolimus;Secondary Objective: - Safety;Primary end point(s): Overall tumor Response Rate, according to Choi criteria at 6 months | — |
Countries
Italy
Outcome results
None listed