Status:
SUSPENDED
Sorafenib in Combination With RAD001 in Advanced Solid Tumors Selected on Molecular Targets
Lead Sponsor:
Southern Europe New Drug Organization
Collaborating Sponsors:
Novartis
Bayer
Conditions:
Advanced Solid Tumors
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
Sorafenib is an oral multikinase inhibitor and among its targets are several RTKs involved in tumor genesis (Raf, Flt-3, c-Kit and RET) and angiogenesis (VEGFR1, 2 and 3 and PDGFRß). Therefore sorafen...
Eligibility Criteria
Inclusion
- Patients with progressive disease of advanced solid tumours judged non suitable for standard treatment
- Biopsiable lesion or archive tissue not older than 1 year to assess the expression of:
- phosphorylated AKT
- phosphorylated p70S6
- RKIP (Raf Kinase Inhibitor Protein)
- phosphorylated ERK1/2 The presence of at least one of the previous targets will be mandatory for patient enrolment
- At least 1 uni-dimensional measurable lesion according to modified RECIST
- Life expectancy of at least 12 weeks
- Age ≥ 18 years old
- ECOG Performance Status of 0 or 1
- Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:
- Haemoglobin ≥9.0 g/dL (5.6 mmol/L)
- Absolute neutrophil count (ANC)≥1.5 x 109/L
- Platelet count ≥100 x 109/L
- Total bilirubin ≤1.5 x upper limit of normal (ULN)
- ALT and AST ≤2.5 x ULN (≤5 x ULN for patients with liver involvement of their cancer)
- Alkaline phosphatase ≤4 x ULN
- PT-INR/PTT \<1.5 x ULN
- Serum albumin levels ≥2.5 mg/dl
- Serum creatinine ≤1.5 x ULN
- HBV/HCV testing in the 2 weeks before treatment start in specific categories of patient with hepatitis B and C risk factors and in additional patients at the discretion of the investigators according to guidelines in Appendix 6.
- All fertile patients must use adequate contraception while on study and for three subsequent months
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures
Exclusion
- History of cardiac disease: congestive heart failure (NYHA II-IV), active coronary artery disease - CAD (MI more than 6 months prior to study entry is allowed), cardiac arrhythmias requiring antiarrhythmic therapy (betablockers or digoxin are permitted) or uncontrolled hypertension
- History of HIV infection or chronic hepatitis B or C
- Patients with NSCLC squamous histotype
- Recurrent hemoptysis or cerebrovascular accident within 12 months, or peripheral vascular disease with claudication on less than 1 block (about 150 metres), or history of clinically significant bleeding non-traumatic
- Deep venous thrombosis or pulmonary embolus within 1 year or ongoing need for full-dose oral or parenteral anticoagulation
- Clinically active infections (\> Grade 2 NCI-CTC AE version 3.0)
- Evidence of CNS tumor metastases
- History of organ allograft
- Pre-existing thyroid abnormality where thyroid function cannot be maintained in the normal range by medication
- Serious, non-healing wound, ulcer, or bone fracture
- Second malignancies within the past 5 years (except for non - melanoma skin cancer and cervical carcinoma in situ)
- Pregnant or breast-feeding patients
- Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Any condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the study
- Patients unable to swallow oral medications
- Any malabsorption condition
- Prior treatment with sorafenib or m-TOR inhibitors
- Ongoing requirement for systemic corticosteroid medication or other immunosuppressants
- Radiotherapy within 3 weeks of start of study drug. Palliative radiotherapy is allowed. Major surgery within 4 weeks of study entry
- Radiotherapy involving \> 30% of the active bone marrow
- Autologous bone marrow transplant or stem cell rescue within 4 months of study entry
- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or planned during the study period
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
Key Trial Info
Start Date :
March 1 2009
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2012
Estimated Enrollment :
45 Patients enrolled
Trial Details
Trial ID
NCT01226056
Start Date
March 1 2009
End Date
December 1 2012
Last Update
October 21 2010
Active Locations (1)
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1
Istituto Europeo di Oncologia,
Milan, Italy, 20141