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Phase I/II Trial With Sorafenib in Combination With RAD001 Administered Orally in Patients With Advanced Solid Tumors, Selected on the Base of Molecular Targets

Phase 1/Phase 2
18 Years
Not Enrolling
Advanced Solid Tumors

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Trial Information

Phase I/II Trial With Sorafenib in Combination With RAD001 Administered Orally in Patients With Advanced Solid Tumors, Selected on the Base of Molecular Targets

Inclusion Criteria:

1. Patients with progressive disease of advanced solid tumours judged non suitable for
standard treatment

2. Biopsiable lesion or archive tissue not older than 1 year to assess the expression

- 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

3. At least 1 uni-dimensional measurable lesion according to modified RECIST

4. Life expectancy of at least 12 weeks

5. Age ≥ 18 years old

6. ECOG Performance Status of 0 or 1

7. 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

- 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

8. 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.

9. All fertile patients must use adequate contraception while on study and for three
subsequent months

10. 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

Exclusion Criteria:

1. 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

2. History of HIV infection or chronic hepatitis B or C

3. Patients with NSCLC squamous histotype

4. 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

5. Deep venous thrombosis or pulmonary embolus within 1 year or ongoing need for
full-dose oral or parenteral anticoagulation

6. Clinically active infections (> Grade 2 NCI-CTC AE version 3.0)

7. Evidence of CNS tumor metastases

8. History of organ allograft

9. Pre-existing thyroid abnormality where thyroid function cannot be maintained in the
normal range by medication

10. Serious, non-healing wound, ulcer, or bone fracture

11. Second malignancies within the past 5 years (except for non - melanoma skin cancer
and cervical carcinoma in situ)

12. Pregnant or breast-feeding patients

13. Substance abuse, medical, psychological, or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results

14. Any condition that is unstable or could jeopardize the safety of the patient and
his/her compliance in the study

15. Patients unable to swallow oral medications

16. Any malabsorption condition

17. Prior treatment with sorafenib or m-TOR inhibitors

18. Ongoing requirement for systemic corticosteroid medication or other

19. Radiotherapy within 3 weeks of start of study drug. Palliative radiotherapy is
allowed. Major surgery within 4 weeks of study entry

20. Radiotherapy involving > 30% of the active bone marrow

21. Autologous bone marrow transplant or stem cell rescue within 4 months of study entry

22. 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

23. Investigational drug therapy outside of this trial during or within 4 weeks of study

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I: Maximum Tolerated Dose (MTD)

Outcome Description:

The maximum tolerated dose (MTD) is defined as the dose in which 2 of 3 or 2 of 6 patients experience a DLT. The Recommended Dose is identified as one dose level below the MTD.

Outcome Time Frame:

6 weeks

Safety Issue:


Principal Investigator

filippo De Braud, MD

Investigator Role:

Study Chair

Investigator Affiliation:

IEO, Milano (Italy)


Italy: Istituto Superiore di Sanità

Study ID:




Start Date:

March 2009

Completion Date:

December 2012

Related Keywords:

  • Advanced Solid Tumors
  • advanced solid tumors
  • Sorafenib (Nexavar®)
  • RAD001 (everolimus)
  • tumor molecular targets
  • Neoplasms