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BARIS - BIBF1120 and RAD001 in Solid Tumors. A Phase I Trial to Evaluate the Safety and Tolerability of Combined BIBF 1120 and RAD001 in Solid Tumors and to Determine the Maximum Tolerated Dose (MTD) of the Combination

Phase 1
18 Years
Open (Enrolling)
Solid Tumors

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Trial Information

BARIS - BIBF1120 and RAD001 in Solid Tumors. A Phase I Trial to Evaluate the Safety and Tolerability of Combined BIBF 1120 and RAD001 in Solid Tumors and to Determine the Maximum Tolerated Dose (MTD) of the Combination

A phase I trial to evaluate the safety and tolerability of combined BIBF 1120 and RAD001 in
solid tumors and to determine the maximum tolerated dose (MTD) of the combination

Inclusion Criteria:

1. Histologically or cytologically proven solid tumor disease after failure of standard
therapy regimen(s)

2. Age > 18 years.

3. ECOG performance status 0 to 1.

4. Life expectancy of at least 12 weeks.

5. Subjects with at least one measurable (CT or MRI) lesion.

6. Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements conducted within 7 days prior to screening:

- Hemoglobin > 9.0 g/dl

- Absolute neutrophil count (ANC) >1,500/mm3

- Platelet count ³ 100,000/μl

- Total bilirubin within normal limits

- ALT and AST < 1.5 x upper limit of normal ( or < 2.5 x upper limit of normal in
patients with liver involvement)

- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically
anticoagulated with an agent such as coumadin or heparin will be allowed to
participate provided that no prior evidence of underlying abnormality in these
parameters exists.]

- Serum creatinine < 1.5 x upper limit of normal or creatinine clearance (CrCl) ≥
50 ml/min calculated by either Cockcroft-Gault or by 24 hours urine collection

7. More than 14 days since previous chemotherapy, radiotherapy and surgery

8. Negative urine or serum HCG in women of childbearing potential

9. Signed and dated informed consent before the start of specific protocol procedures

Exclusion Criteria:

1. Limited number of prior lines of treatment (including surgery and radiotherapy, if
part of the standard therapy of the respective tumor entity)

2. Prior treatment with BIBF 1120 or any other VEGFR inhibitor (bevacizumab is allowed)

3. Prior treatment with RAD001 or any other mTOR inhibitor

4. Known hypersensitivity to the trial drugs, to their excipients or to contrast media

5. Chemo-, hormono-, radio-(except for brain and extremities) or immunotherapy or
therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the
past 2 weeks prior to treatment with the trial drugs

6. Persistence of clinically relevant therapy related toxicity from previous chemo
and/or radiotherapy

7. Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment
with radiotherapy, symptomatic, requiring treatment with anticonvulsants;
dexamethasone therapy will be allowed if administered as stable dose for at least one
month before trial drug administration) or leptomeningeal metastases (documented by
lumbar puncture)

8. History of cardiac disease: congestive heart failure >NYHA class 2; active coronary
artery disease (CAD), (MI more than 6 mo prior to study entry is allowed); cardiac
arrhythmias requiring antiarrhythmic therapy (beta blockers or digoxin are permitted)
or uncontrolled hypertension

9. Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of BIBF1120 or RAD001 (e.g. ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel

10. History of HIV infection or previously seropositive for the virus

11. History of Hepatitis B or/and C or previously seropositive for the Hepatitis B or/and
C virus

12. Radiographic evidence of cavitary or necrotic tumors

13. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of
major blood vessels

14. Treatment with other investigational drugs or treatment in another clinical trial
within the past 30 days before start of therapy or concomitantly with the trial

15. Patients with seizure disorder requiring enzyme-inducing antiepileptics

16. Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed
for maintenance of an indwelling intravenous devise) or antiplatelet therapy (except
for low-dose therapy with acetylsalicylic acid ≤325mg per day)

17. Major injuries within the past 10 days prior to start of study treatment with
incomplete wound healing and/or planned surgery during the on-treatment study period

18. Evidence or history of bleeding diasthesis or thrombosis, and known inherited
predisposition to bleeding or thrombosis

19. Proteinuria CTC AE grade 2 or greater

20. Active serious infections

21. Patients undergoing renal dialysis

22. Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively
treated > 3 years prior to study entry

23. Serious illness or concomitant non-oncological disease such as neurologic,
psychiatric, infectious disease or active ulcers (gastrointestinal tract, skin) or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration and in the judgment of the investigator would make the
patient inappropriate for entry into the study

24. Patients who are sexually active and unwilling to use a medically acceptable method
of contraception (e.g. such as implants, injectables, combined oral contraceptives,
some intrauterine devices or vasectomized partner for participating females, condoms
for participating males) during the trial and for at least three months after end of
active therapy

25. Pregnancy or breast feeding

26. Psychological, familial, sociological or geographical factors potentially hampering
compliance with the study protocol and follow-up schedule

27. Active alcohol or drug abuse

Type of Study:


Study Design:

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

Outcome Measure:

To determine the maximum tolerated dose (MTD) of RAD001 in combination with BIBF 1120 (150mg bid or 200mg bid) (endpoint: dose-limiting toxicities)

Outcome Description:

Documentation an estimation of adverse events

Outcome Time Frame:

Every visit

Safety Issue:


Principal Investigator

Juergen Wolf, Prof.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital of Cologne


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

July 2012

Completion Date:

March 2015

Related Keywords:

  • Solid Tumors
  • Solid Tumors
  • Neoplasms