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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of Cologne
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Prof. Dr. Juergen Wolf, Lung Cancer Group Cologne
ClinicalTrials.gov Identifier:
NCT01349296
First received: May 5, 2011
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

BIBF1120 and RAD001 in solid tumors


Condition Intervention Phase
Solid Tumors
Drug: Everolimus + BIBF 1120
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Cologne:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Documentation an estimation of adverse events

  • 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 ] [ Designated as safety issue: Yes ]
    Documentation an estimation of adverse events


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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


  • 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 ] [ Designated as safety issue: No ]
    Blood collection for pharmacokinetic analysis

  • 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 ] [ Designated as safety issue: No ]
    DCE MRI will be done

  • To correlate the clinical outcome with FGFR1-amplification status (endpoints: see above for clinical parameters) [ Time Frame: Screening ] [ Designated as safety issue: No ]
    Documentation of histology


Estimated Enrollment: 18
Study Start Date: July 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01349296

Contacts
Contact: Matthias Scheffler, MD 0049221478 ext 86147 matthias.scheffler@uk-koeln.de
Contact: Lucia Nogova, MD 0049221478 ext 87033 lucia.nogova@uk-koeln.de

Locations
Germany
University Hospital of Cologne Recruiting
Cologne, NRW, Germany, 50937
Contact: Matthias Scheffler, MD    0049221478 ext 86127    matthias.scheffler@uk-koeln.de   
Contact: Irini Papachristou    0049221 ext 99741672    irini.papachristou@uk-koeln.de   
Sponsors and Collaborators
University of Cologne
Boehringer Ingelheim
Investigators
Principal Investigator: Juergen Wolf, Prof. University Hospital of Cologne
  More Information

No publications provided

Responsible Party: Prof. Dr. Juergen Wolf, Prof. Dr., Lung Cancer Group Cologne
ClinicalTrials.gov Identifier: NCT01349296     History of Changes
Other Study ID Numbers: BARIS
Study First Received: May 5, 2011
Last Updated: June 18, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Cologne:
Solid Tumors

Additional relevant MeSH terms:
Neoplasms
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 26, 2014