BIBF 1120 and RAD001 in Solid Tumors - Phase I (BARIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01349296
Recruitment Status : Completed
First Posted : May 6, 2011
Last Update Posted : May 20, 2016
Boehringer Ingelheim
Information provided by (Responsible Party):
Prof. Dr. Juergen Wolf, Lung Cancer Group Cologne

Brief Summary:
BIBF1120 and RAD001 in solid tumors

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Everolimus + BIBF 1120 Phase 1

Detailed Description:
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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2012
Actual Primary Completion Date : October 2014
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BIBF 1120 + RAD001 Drug: Everolimus + BIBF 1120
Dose level 1: 1x 5mg Everolimus/d + 2x 150mg BIBF 1120/d. Dose level 2: 1x 5mg Everolimus/d + 2x 200mg BIBF 1120/d. Dose level 3: 1x 10mg Everolimus/d + 2x 200mg BIBF 1120/d
Other Name: Everolimus, RAD001, Afinitor, BIBF 1120

Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) of RAD001 in combination with BIBF 1120 (150mg bid or 200mg bid) (endpoint: dose-limiting toxicities) [ Time Frame: Every visit ]
    Documentation an estimation of adverse events

  2. To evaluate the tolerability of BIBF1120 and RAD001 in combination (endpoints: assessment of adverse events (AEs) according to CTC-AE V4.0) [ Time Frame: Every visit during the study ]
    Documentation an estimation of adverse events

Secondary Outcome Measures :
  1. To evaluate the clinical efficacy of the combination descriptively (endpoints: RR, progression free survival (PFS), overall survival (OS)) [ Time Frame: Baseline and every six weeks during the study, after study every 6 months ]

    CT will be done for evaluation of RR and PFS on day 57 and then every 6 weeks until progression.

    For overall survival a telephone call every six months after study is continuation will be done

  2. To analyze individual BIBF1120 pharmacokinetic (PK) parameters at steady-state (ss) of monotherapy and PK parameters of both BIBF1120 and RAD001 at ss of combination [ Time Frame: day 14, day 29 ]
    Blood collection for pharmacokinetic analysis

  3. To assess changes in tumor vasculature a) early under BIBF1120 monotherapy, b) at ss of BIBF1120 monotherapy and c) at ss of combination therapy using dynamic contrast-enhanced MRI (DCE-MRI) (endpoints: IAUC, Ktrans, Kep, Ve) [ Time Frame: baseline, day 3, day 14, day 29 ]
    DCE MRI will be done

  4. To correlate the clinical outcome with FGFR1-amplification status (endpoints: see above for clinical parameters) [ Time Frame: Screening ]
    Documentation of histology

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 resection)
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01349296

University Hospital of Cologne
Cologne, NRW, Germany, 50937
Sponsors and Collaborators
University of Cologne
Boehringer Ingelheim
Principal Investigator: Juergen Wolf, Prof. University Hospital of Cologne

Responsible Party: Prof. Dr. Juergen Wolf, Prof. Dr., Lung Cancer Group Cologne Identifier: NCT01349296     History of Changes
Other Study ID Numbers: BARIS
First Posted: May 6, 2011    Key Record Dates
Last Update Posted: May 20, 2016
Last Verified: May 2016

Keywords provided by Prof. Dr. Juergen Wolf, Lung Cancer Group Cologne:
Solid Tumors

Additional relevant MeSH terms:
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action