A phase II, open label study to evaluate the activity and safety of Everolimus in association to Imatinib in PDGFRA-D842V unresectable or metastatic gastrointestinal stromal tumours (GISTs)as first line treatment - ND

Conditions: patients with unresectable and/or metastatic gastrointestinal stromal tumours with exon 18 PDGFRA mutation
MedDRA version: 12.1Level: LLTClassification code 10051066Term: Gastrointestinal stromal tumour

Registration Number: EUCTR2010-020305-32-IT

Lead Sponsor: ISTITUTO NAZIONALE PER LA CURA TUMORI

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

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 < 2 x ULN, BUN < 25 mg/dl, serum AST (SGOT), ALT (SGPT) < 2.5 X ULN and bilirubin < 1.5 X ULN. - Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study and for up to 8 weeks after last dose of study drug. Because oral, implantable or injectable contraceptives may be affected by cytochrome P450 interactions, an appropriate method of birth control should be used throughout the trial in both sexes. - Ability to understand and willingness to sign a written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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