advanced cancer Advanced solid tumor
Conditions
Interventions
Eligible subjects will receive three intramuscular injections with
hVEGF26-104/RFASE in dose-escalation on days 0 (primer), 14 and 28 (boosters),
followed by an observation period of 6 weeks. Blood
the patient will receive another booster of hVEGF26-104/RFASE in order to
achieve VEGF neutralization again.
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed advanced, solid malignancy. 2. Refractory or not amenable to standard therapy 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Willing and able to give written informed consent 5. Patient is * 18 years of age at the time of signature of the informed consent 6. Adequate hematological function: Absolute neutrophil count (ANC) * 1.5 x 109/L, platelets * 100 x 109/L, Hemoglobin * 6.0 mmol/L. 7. Adequate hepatic function: serum bilirubin * 1.5 times the upper limit of normal (ULN), ALT and AST * 2.5 x ULN (or * 5 times ULN if liver metastases are present). 8. Adequate renal function: eGFR * 50ml/min 9. PT-INR/PTT
Exclusion criteria
Exclusion criteria: 1. Major surgery within 28 days before the initiation of study treatment 2. Any serious non-healing wounds, ulcers, or bone fractures within 28 days prior to the initiation of study treatment. 3. Deep venous thrombosis (DVT) or pulmonary embolus (PE) within 1 year prior to the initiation of study treatment. 4. Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) 5. The patient is scheduled to receive another vaccination during the DLT period. 6. A previous serious allergic reaction to a vaccine such as angioedema and anaphylaxis. 7. Treatment with bevacizumab within 6 weeks prior to the initiation of study treatment. 8. Uncontrolled auto-immune diseases 9. Primary or secondary immunodeficiency, including HIV 10. Treatment with a glucocorticoid derivative in an equivalent dose of * 10mg prednisone a day. 11. Female patients: the patient is pregnant or lactating. 12. When the patient is scheduled to receive any other anticancer treatments. 13. Chemotherapy within 28 days prior to the initiation of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Safety and tolerability of hVEGF26-104/RFASE, measured by the number of participants with serious and non-serious adverse events - Neutralization of endogenous VEGF in serum, defined as a VEGF level below 9.0 pg/mL as determined by sandwich ELISA. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Anti-VEGF antibody titer in serum, plasma and a platelet sample, as determined by indirect ELISA. - VEGF concentration in plasma as determined by sandwich ELISA. - VEGF concentration in a platelet sample as determined by sandwich ELISA. - Functional VEGF neutralization, as determined in a Ba/F3-R2-R2 cell proliferation bio-assay. - Cellular (T-cell) immune response, as determined by ELISPOT - Immune modulation - Angiogenesis suppression: Within the tumor, by assessing microvessel density (MVD), quantity of proliferating endothelial cells and pericyt coverage. | — |
Countries
Netherlands
Outcome results
None listed