Reduction of Plasma Free VEGF-A Using Low-dose Bevacizumab in Hemodialysis Patients

• Status: Withdrawn
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary purpose of this pilot study is to assess the pharmacokinetic profile of low-dose bevacizumab and its effectiveness in reducing plasma free VEGF-A levels safely in hemodialysis patients. This information will be used to plan a phase 1 clinical trial evaluating bevacizumab's role in hemodialysis vascular access failure.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Treatments: Bevacizumab; Endothelial Growth Factors

Criteria

Inclusion Criteria

• Patients between 18 and 85 years old, inclusive

• Patients with end stage renal disease (ESRD) who are currently undergoing hemodialysis treatment through an upper extremity fistula

• Hemoglobin ≥8g/dL and platelet count ≥100,000/mm3 prior to Day 1

• Adequate liver function, defined as serum bilirubin ≤1.5 mg/dL; gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase ≤2x upper limit of normal or international normalized ratio (INR) ≤ 1.5 prior to Day 0 or INR ≤ 2 if on anticoagulant therapy.

• Ability to communicate meaningfully with investigative staff, competence to give written informed consent, and ability to comply with entire study procedures

• If female and of childbearing years, must have a negative serum pregnancy test at the screening visit (Visit 1). Both female patients of childbearing potential and male patients with childbearing potential partners must be willing to use contraception from the time of screening to completion of the study

• Life expectancy of at least 1 year

Exclusion Criteria

• Known sensitivity to bevacizumab or prior treatment with any medication known to target VEGF

• Current use of medications that are known to interact with the safety and efficacy of bevacizumab (most commonly: Antineoplastics (Anthracyclines), Belimumab, Bisphosphonate Derivatives, Clozapine, Dipyrone, Irinotecan, Sorafenib, and Sutent)

• History or evidence of severe cardiac disease (NYHA Functional Class III or IV), myocardial infarction within six months of study entry (Day 1), ventricular tachyarrhythmias requiring continuing treatment, or unstable angina

• Significant uncontrolled hypertension (systolic blood pressure above 160 mm Hg and/or diastolic blood pressure above 100 mm Hg);

• Stroke within six (6) months of study entry (Day 1)

• Treatment with any investigational drug/ device within 60 days prior to study entry (Day1)

• Treatment with vitamin K-antagonists or direct thrombin inhibitors with an INR ≥2

• All patients (including both female patients of childbearing potential and male patients with childbearing potential partners) who do not use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly), e.g. implants, injectables, combined oral contraceptives in combination with a barrier method, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner

• Malignancy or treatment for malignancy within the previous 6 months

• Immunodeficiency including AIDS / HIV or Active autoimmune disease

• Documented hypercoagulable state or history of 2 or more deep vein thromboses (DVTs) or other spontaneous intravascular thrombotic events

• Bleeding diathesis or Anemia with a hematocrit level of less than 30%

• A prothrombin time or a partial thromboplastin time more than 1.2 times the upper limit of normal, or absolute platelet counts below the lower limit of normal; an absolute neutrophil count below 1,500/mm3

• Active local or systemic infection (WBC > 15,000/mm3)

• Gastrointestinal ulcer or bleeding, or wound dehiscence

• Scheduled elective surgery within 2 months of start date

• Known serious allergy to aspirin or penicillin

• Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of bevacizumab

• Employees of the sponsor or patients who are employees or relatives of the investigator