Clinical trial NCT01141257: Study of Angiocal® in Patients With Solid Tumors, Investigating Safety, Tolerability, Blood Concentration of Study Drug
Official title: A Phase I, Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Angiocal® (PRS-050-PEG40) in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Angiocal®; PRS-050-PEG40; Solid tumor; Phase I
Lead sponsor: Pieris Pharmaceuticals GmbH
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
First posted: 2010-06-10
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if Angiocal® (PRS-050-PEG40) is safe and well tolerated when it is injected into the veins of patients with solid tumors. Other purposes of this study are to investigate how the body of the patients reacts to Angiocal®, how the blood level of Angiocal® develops after injection and how the tumor responds to the injection of Angiocal®.

Detailed description: This is a phase I, open-label, dose escalation study with Angiocal® in patients with solid tumors using a group sequential adaptive treatment assignment. Patients will be allocated to different dose levels in small cohorts and will receive one single dose application on Day 1, followed by a repeated dosing period. The primary objective of the study is to evaluate the safety and tolerability of Angiocal® when administered intravenously to patients with solid tumors. The secondary objectives of the study are the characterization of the pharmacodynamic response, evaluation of the pharmacokinetic profile of Angiocal®, observation of tumor response.

Eligibility criteria: Inclusion Criteria:

* Males or females with advanced, recurrent or metastatic cancer, refractory to standard therapy;
* Age ≥18 years;
* Signed informed consent form and ability to understand the study procedures.

Exclusion Criteria:

* Concomitant anticancer therapy, including radiation;
* Current or previous (within 30 days of first study dosing) treatment with another investigational drug or participation in another clinical study;
* Chronic daily treatment with aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day);
* Chronic daily treatment with corticosteroids, with the exception of inhaled steroids;
* Inadequate bone marrow function;
* Inadequate liver function;
* Inadequate renal function;
* Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) \>1.5 or an activated partial thromboplastin time (aPTT) \>1.5 x ULN within 7 days prior to first study treatment;
* Patients with lymphomas;
* Evidence of spinal cord compression or brain metastases;
* Other malignancy diagnosed within the previous 5 years;
* Pregnant or lactating females.;
* All patients who do not use a highly effective method of birth control;
* Major surgical procedure (including open biopsy) within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment;
* Minor surgical procedures, within 24 hours prior to the first study treatment;
* History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding;
* Uncontrolled hypertension or clinically significant (i.e. active) cardiovascular disease;
* History of abdominal fistula, grade 4 bowel obstruction or gastrointestinal perforation, intra-abdominal abscess within 6 months of enrollment;
* Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel;
* Serious non-healing wound, peptic ulcer or bone fracture;
* Known hypersensitivity to the study medication or any of its excipients;
* Evidence of any other medical conditions that may interfere with the planned treatment, affect patient compliance or place the patient at high risk of treatment-related complications;
* Previous enrollment in this study;
* Known hepatitis B or C or HIV infection;
* Employees of the sponsor or patients who are employees or relatives of the investigator.

Primary outcomes:
measure: Dose limiting toxicity
timeFrame: Throughout the course of the study
Secondary outcomes:
measure: Pharmacokinetic analysis
timeFrame: Throughout the course of the study
measure: Development of biomarkers in blood over time
timeFrame: Throughout the course of the study
measure: Response of target lesions over time
timeFrame: Throughout the course of the study
measure: ECOG performance status
timeFrame: Throughout the course of the study
measure: Clinical laboratory measures
timeFrame: Throughout the course of the study
measure: Anti-drug antibodies
timeFrame: Throughout the course of the study
measure: Results of 12-lead Electrocardiogram by time point
timeFrame: Throughout the course of the study
measure: Changes of vital signs from the baseline visit
timeFrame: Throughout the course of the study
measure: Physical examination
timeFrame: Throughout the course of the study
Other outcomes:
Locations:
city: Breisgau
country: Germany
state: Baden-Württemberg
city: Ruhrgebiet
country: Germany
state: Nordrhein-Westfalen
Study officials:
affiliation: Pieris Pharmaceuticals GmbH
name: Laurent Audoly, PhD
role: STUDY_DIRECTOR
References:
citation: Mross K, Richly H, Fischer R, Scharr D, Buchert M, Stern A, Gille H, Audoly LP, Scheulen ME. First-in-human phase I study of PRS-050 (Angiocal), an Anticalin targeting and antagonizing VEGF-A, in patients with advanced solid tumors. PLoS One. 2013 Dec 13;8(12):e83232. doi: 10.1371/journal.pone.0083232. eCollection 2013.