Phase I Study on VEGF Vaccination in Metastatic Solid Tumors
Metastatic Cancer
About this trial
This is an interventional treatment trial for Metastatic Cancer focused on measuring VEGF, Vaccine, Angiogenesis
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed advanced, solid malignancy.
- Refractory or not amenable to standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Please refer to Appendix II for more information.
- Willing and able to give written informed consent
- Patient is ≥ 18 years of age at the time of signature of the informed consent
- Adequate hematological function: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hemoglobin ≥ 6.0 mmol/L.
- 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).
- Adequate renal function: eGFR ≥ 50ml/min
- PT-INR/PTT < 1.5 x ULN, unless coumarin derivatives are used
- Activated partial thromboplastin time (APTT) < 1.25 x ULN (therapeutic anticoagulation therapy is allowed, if this treatment can be interrupted for a biopsy as judged by the treating physician)
Female patients of childbearing potential may be enrolled in the study, if the patient
- Has practiced adequate contraception for 30 days prior to first hVEGF26-104/RFASE administration.
- Negative pregnancy test
- Has agreed to continue adequate contraception for as long as VEGF is neutralized.
Exclusion Criteria:
- Major surgery within 28 days before the initiation of study treatment
- Any serious non-healing wounds, ulcers, or bone fractures within 28 days prior to the initiation of study treatment.
- Deep venous thrombosis (DVT) or pulmonary embolus (PE) within 1 year prior to the initiation of study treatment.
- Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg)
- The patient is scheduled to receive another vaccination during the DLT period.
- A previous serious allergic reaction to a vaccine such as angioedema and anaphylaxis.
- Treatment with bevacizumab within 6 weeks prior to the initiation of study treatment.
- Uncontrolled auto-immune diseases
- Primary or secondary immunodeficiency, including HIV
- Treatment with a glucocorticoid derivative in an equivalent dose of ≥ 10mg prednisone a day.
- Female patients: the patient is pregnant or lactating.
- When the patient is scheduled to receive any other anticancer treatments.
- Chemotherapy within 28 days prior to the initiation of study treatment.
Sites / Locations
- VU University Medical Center
Arms of the Study
Arm 1
Experimental
hVEGF26-104/RFASE vaccination
hVEGF26-104/RFASE is investigated in dose escalation in which hVEGF26-104 is escalated from 62.5 ug to 500 ug and RFASE is given in a fixed dose of 20 mg. Three patients are treated at each dose level. If 0 of the 3 patients are observed to have DLT, the dose level is escalated one step for the next cohort. If 1 of the 3 patients shows DLT, 3 additional patients are treated at that dose level. If none of these show DLT, the dose level is escalated for the next cohort; otherwise, the prior dose level is defined as the MTD. At the highest dose level 6 patients will be treated. The recommended dose for a phase II trial will be the lowest dose that results in the most effective VEGF neutralization, together with acceptable safety and toxicity.