An Dose Escalation Study of BIBF 1120 Administered in Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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Maximum tolerated dose (MTD), safety, pharmacokinetics, efficacy of BIBF 1120, pharmacodynamics

Official Title
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An Open Label Dose Escalation Study of BIBF 1120 Administered Orally for Four Weeks in Patients With Relapsed or Refractory Multiple Myeloma With Repeated Administration in Patients With Clinical Benefit

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: BIBF 1120 ES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with confirmed diagnosis of multiple myeloma, who did not respond to or relapsed after either anthracyclines and pulsed glucocorticoids or high-dose therapy and who are currently not eligible for transplant modalities. Age 18 years or older Life expectancy of at least six months Patients have to give written informed consent (which must be consistent with ICH-GCP and local legislation) Eastern Cooperative Oncology Group (ECOG) performance score <2. Recovery from all therapy-related toxicities from previous chemo-, immuno- or radiotherapies. Exclusion Criteria: History of relevant surgical procedures during the last four weeks prior to treatment with the trial drug, or active ulcers, fractures or injuries with incomplete healing Active infectious disease Uncontrolled, severe hypertension Gastrointestinal disorders anticipated to interfere with the resorption of the study drug Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol Absolute neutrophil count less than 1000 / mm³. Platelet count less than 30 000 / mm³ Conjugated Bilirubin greater than 2 mg / dl (> 34 μmol/L, SI unit equivalent) Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than three times the upper limit of normal Endogenous creatinine clearance (ECC) <20 ml/min Women and men who are sexually active and unwilling to use a medically acceptable method of contraception Pregnancy or breastfeeding Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug) Patients unable to comply with the protocol Active alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBF 1120<br> | Drug: BIBF 1120 ES<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) |  | Up to 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and intensity of adverse events according to Common Toxicity Criteria (CTC) associated with increasing doses of BIBF 1120 |  | Up to 11 months | 
| Change from baseline in laboratory parameters |  | Baseline, up to 11 months | 
| Objective tumor response in surrogate markers |  | Baseline, up to 11 month | 
| Concentration at 2h (C2,1) |  | 2 hours after first administration | 
| Change from baseline in cellular protein tyrosine kinase inhibition |  | Baseline, up to 11 months | 
| Change from baseline in Eastern Cooperative Oncology Group (ECOG) performance score |  | Baseline, up to 11 months | 
| Change in vital signs |  | up to 11 months | 
| Change from baseline in electrocardiogram (ECG) |  | Baseline, up to 11 months | 
| Predose concentration immediately before administration of the Nth dose over the dosing interval τ (Cpre,N) |  | Up to day 28 | 
| Area under the plasma concentration-time curve during the dosing interval τ (24 h) at steady state (AUCτ,ss) |  | Up to 11 months | 
| Plasma concentration at the time point immediately before dosing at steady state (Cpre,ss) |  | Up to 11 months | 
| Minimum plasma concentration during the dosing interval τ at steady state (Cmin,ss) |  | Up to 11 months | 
| Maximum plasma concentration during the dosing interval τ at steady state (Cmax,ss) |  | Up to 11 months | 
| Time to reach minimum plasma concentration during the dosing interval τ at steady state (tmin,ss) |  | Up to 11 months | 
| Time to reach maximum plasma concentration during the dosing interval τ at steady state (tmax,ss) |  | Up to 11 months | 
| Terminal half-life at steady state (t1/2,ss) |  | Up to 11 months | 
| Apparent plasma clearance at steady state (CL/F,ss) |  | Up to 11 months | 
| Mean residence time at steady state (MRTpo,ss) |  | Up to 11 months | 
| Apparent volume of distribution during the terminal phase at steady state (Vz/F,ss) |  | Up to 11 months | 
| Tumor response assessed according to the European Group for Blood and Marrow Transplantation (EBMT) criteria |  | Up to 11 months |