An Dose Escalation Study of BIBF 1120 Administered in Patients With Relapsed or Refractory Multiple Myeloma
Phase 1
Completed
- Conditions
- Multiple Myeloma
- Interventions
- Drug: BIBF 1120 ES
- Registration Number
- NCT02182141
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Maximum tolerated dose (MTD), safety, pharmacokinetics, efficacy of BIBF 1120, pharmacodynamics
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BIBF 1120 BIBF 1120 ES -
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) Up to 11 months
- Secondary Outcome Measures
Name Time Method Change from baseline in laboratory parameters Baseline, up to 11 months Concentration at 2h (C2,1) 2 hours after first administration Change from baseline in Eastern Cooperative Oncology Group (ECOG) performance score 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 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 Objective tumor response in surrogate markers Baseline, up to 11 month Change from baseline in electrocardiogram (ECG) Baseline, up to 11 months Change from baseline in cellular protein tyrosine kinase inhibition Baseline, up to 11 months 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 Incidence and intensity of adverse events according to Common Toxicity Criteria (CTC) associated with increasing doses of BIBF 1120 Up to 11 months Change in vital signs up to 11 months Maximum plasma concentration during the dosing interval τ at steady state (Cmax,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