Clinical trial NCT01951846: To Determine the Maximum Tolerated Dose (MTD) of BIBF 1120 in Patients With Solid Tumours
Official title: An Open Label Dose Escalation Study of BIBF 1120 Administered Orally for Four Weeks in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Solid Tumour
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-09-27
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: The primary objective of this study was to determine the maximum tolerated dose (MTD) of BIBF 1120 in patients with solid tumours by the monitoring of drug-related adverse events. Secondary objectives were the evaluation of safety, efficacy, pharmacokinetics, and pharmacodynamics.


Eligibility criteria: Inclusion Criteria:

* Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
* Evaluable tumour deposits by one or more techniques (X-ray, CT, MRI, ultrasound)
* Age 18 years or older
* Life expectancy of at least three months
* Patients had to give written informed consent (which must be consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) and local legislation)
* Eastern Cooperative Oncology Group (ECOG) performance score \< 2
* Full recovery from all therapy-related toxicities from previous chemo-, hormone-,immuno-, or radiotherapy

Exclusion Criteria:

* History of relevant surgical procedures during the last four weeks prior to treatment with the trial drug, or active ulcers, or injuries with incomplete wound healing
* Pregnancy or breastfeeding
* Active infectious disease
* Brain metastases requiring therapy
* Absolute neutrophil count less than 1500 / mm3
* Platelet count less than 100 000 / mm3
* Bilirubin greater than 1.5 mg / dl (\> 26 μmol / L, International System of Units (SI unit) equivalent)
* Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
* Serum creatinine greater than 1.5 mg / dl (\> 132 μmol / L, SI unit equivalent)
* 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
* Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
* 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

Primary outcomes:
measure: Maximum tolerated dose of BIBF 1120
timeFrame: up to 30 days
Secondary outcomes:
measure: Overall best investigator assessment of tumour response
timeFrame: up to 4 months
measure: Overall best calculated assessment of tumour response
timeFrame: up to 4 months
measure: Time to tumour progression
timeFrame: up to 4 months
measure: Change in Eastern Cooperative Oncology Group (ECOG) score
timeFrame: up to 4 months
measure: Number of patients with response in transfer of contrast medium into tissue (Ktrans)
timeFrame: up to 4 months
measure: Number of patients with response in initial area under the curve for first 60 seconds after onset of gadolinium uptake (iAUC60)
timeFrame: 60 seconds
measure: Mean plasma level of vascular endothelial growth factor (VEGF)
timeFrame: 10 hours after drug intake
measure: Mean plasma level of basic fibroblast growth factor (bFGF)
timeFrame: 10 hours after drug intake
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Klinik für Tumorbiologie, Abteilung Internistische Onkologie
Study officials:
References: