Advanced solid tumors MedDRA version: 16.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: hVEGF26-104
Pharmaceutical Form: Solution for injection
INN or Proposed INN: hVEGF26-104
Current Sponsor code: hVEGF26-104
Concentration unit: µg/ml microgram(s)/millilitre
Concentration
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion 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. - 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 - Female patients of childbearing potential may be enrolled in the study, if the patient o Has practiced adequate contraception for 30 days prior to first hVEGF26-104/RFASE administration. o Negative pregnancy test o Has agreed to continue adequate contraception for as long as VEGF is neutralized. - Part 2 only: o Histological confirmed advanced colorectal cancer o Planning to initiate treatment with irinotecan or o Planning to initiate second line treatment with the XELOX regimen after progression on first line treatment with XELOX combined with bevacizumab. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
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. - Primary or secondary immunodeficiency - Treatment with a glucocorticoid derivative in an equivalent dose of = 10mg prednisone a day. - Female patients: the patient is pregnant or lactating. - Part 1 only: o When the patient is scheduled to receive any other anticancer treatments than those specified in the protocol. o Chemotherapy within 28 days prior to the initiation of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: The primary objectives of the study are: -To investigate the safety and tolerability profile of the therapeutic vaccine hVEGF26-104/RFASE. -To determine the effective dose of hVEGF26-104/RFASE required to neutralize VEGF in serum, defined as a VEGF level below 9,0 pg/mL. Part 2: -To investigate the safety and VEGF neutralizing ability of hVEGF26-104/RFASE combined with irinotecan chemotherapy in a metastatic colorectal cancer expansion cohort. -To investigate the safety and VEGF neutralizing ability of hVEGF26-104/RFASE combined with the XELOX regimen (capecitabine plus oxaliplatin) in a metastatic colorectal cancer expansion cohort. ;Secondary Objective: The secondary objectives of the study are to investigate: -The anti-VEGF antibody titer, induced by hVEGF26-104/RFASE administration. -To determine the effective dose of hVEGF26-104/RFASE required to neutralize VEGF in plasma and in a platelet sample. -The effect of VEGF neutralization in a functional Ba/F3-R2 cell proliferation assay. The exploratory objectives of the study are: -To assess the cellular anti-tumor immune response upon hVEGF26-104/RFASE administration. -To assess immunomodulatory effects upon hVEGF26-104/RFASE administration. -To make a preliminary assessment of hVEGF26-104/RFASE to suppress angiogenesis within the tumor. -To assess the immune infiltration and the regulation of endothelial cell adhesion molecules in the tumor. ;Primary end point(s): Part 1: 1. Safety and tolerability of hVEGF26-104/RFASE. 2. Neutralization of endogenous VEGF in serum, defined as a VEGF level below 9,0 pg/mL as determined by sandwich ELISA. Part 2: 1. Safety and tolerability of hVEGF26-104/RFASE in combination with different chemotherapy regimens. 2. Neutralization of endogenous VEGF in serum, defined as a VEGF level below 9,0 pg/mL as determined by sandwich ELISA. ;Timepoint(s) of evaluation of this end point: 1. Safety and tolerability will be assessed at each treatment visit. The D | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: Secondary end points 1. Anti-VEGF antibody titer in serum, plasma and a platelet sample, as determined by indirect ELISA. 2. VEGF concentration in plasma as determined by sandwich ELISA. 3. VEGF concentration in a platelet sample as determined by sandwich ELISA. 4. Functional VEGF neutralization, as determined in a Ba/F3-R2-R2 cell proliferation bio-assay. Exploratory end points 1. Cellular (T-cell) immune response, as determined by ELISPOT 2. Immune modulation 3. Angiogenesis suppression within the tumor, by assessing microvessel density (MVD), quantity of proliferating endothelial cells and pericyt coverage. ;Timepoint(s) of evaluation of this end point: Secondary end points 1. Will be assessed at each treatment visit 2. Will be assessed at each treatment visit 3. Will be assessed at each treatment visit 4. Will be assessed at each treatment visit Exploratory end points 1. Will be assessed at day 0, week 4, week 10 and week 26 2. Will be assessed at day 0, week 10, week 10 and week 26 3. Will be assessed at day 0 and week 10 | — |
Countries
Netherlands
Contacts
Public ContactSecretary Medical Oncology
VU University Medical Center
Outcome results
None listed