BIBF 1120 and RAD001 in Solid Tumors - Phase I

NCT01349296 | Completed Phase 1 DMC

• 1 other identifier: BARIS
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

BIBF1120 and RAD001 in solid tumors

Conditions

Solid Tumors

Keywords

Solid Tumors

Outcome Measures

Primary Outcomes (2)

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

  Documentation an estimation of adverse events

  Every visit

• To evaluate the tolerability of BIBF1120 and RAD001 in combination (endpoints: assessment of adverse events (AEs) according to CTC-AE V4.0)

  Documentation an estimation of adverse events

  Every visit during the study

Secondary Outcomes (4)

• To evaluate the clinical efficacy of the combination descriptively (endpoints: RR, progression free survival (PFS), overall survival (OS))

  Baseline and every six weeks during the study, after study every 6 months

• 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

  day 14, day 29

• 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)

  baseline, day 3, day 14, day 29

• To correlate the clinical outcome with FGFR1-amplification status (endpoints: see above for clinical parameters)

  Screening

Study Arms (1)

BIBF 1120 + RAD001

EXPERIMENTAL

Drug: Everolimus + BIBF 1120

Interventions

Everolimus + BIBF 1120 DRUG

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

Also known as: Everolimus, RAD001, Afinitor, BIBF 1120

BIBF 1120 + RAD001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven solid tumor disease after failure of standard therapy regimen(s)
• Age \> 18 years.
• ECOG performance status 0 to 1.
• Life expectancy of at least 12 weeks.
• Subjects with at least one measurable (CT or MRI) lesion.
• 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
• More than 14 days since previous chemotherapy, radiotherapy and surgery
• Negative urine or serum HCG in women of childbearing potential

You may not qualify if:

• Limited number of prior lines of treatment (including surgery and radiotherapy, if part of the standard therapy of the respective tumor entity)
• Prior treatment with BIBF 1120 or any other VEGFR inhibitor (bevacizumab is allowed)
• Prior treatment with RAD001 or any other mTOR inhibitor
• Known hypersensitivity to the trial drugs, to their excipients or to contrast media
• 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
• Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy
• 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)
• 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
• 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)
• History of HIV infection or previously seropositive for the virus
• History of Hepatitis B or/and C or previously seropositive for the Hepatitis B or/and C virus
• Radiographic evidence of cavitary or necrotic tumors
• Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
• 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
• Patients with seizure disorder requiring enzyme-inducing antiepileptics

Sponsors & Collaborators

• University of Cologne: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

University Hospital of Cologne

Cologne, North Rhine-Westphalia, 50937, Germany

Location

MeSH Terms

Interventions

Everolimus; nintedanib

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Juergen Wolf, Prof.

  University Hospital of Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: May 5, 2011
• First Posted: May 6, 2011
• Study Start: July 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: May 1, 2016
• Last Updated: May 20, 2016

Record last verified: 2016-05

Locations

DE (1)