Phase I Study on VEGF Vaccination in Metastatic Solid Tumors

NCT02237638 | Completed Phase 1 DMC

• 1 other identifier: NL45279.000.13
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to investigate the safety and tolerability profile of the therapeutic vaccine hVEGF26-104/RFASE and 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.

Conditions

Metastatic Cancer

Keywords

VEGF; Vaccine; Angiogenesis

Outcome Measures

Primary Outcomes (3)

• Number of participants with serious and non-serious adverse events

  10-12 weeks

• Neutralization of endogenous VEGF in serum

  VEGF neutralization is defined as a VEGF level below 9,0 pg/mL as determined by sandwich ELISA.

  10-12 weeks

• Maximum tolerated dose (MTD) of hVEGF26-104/RFASE

  10-12 weeks

Secondary Outcomes (3)

• Calculation of the anti-VEGF antibody titer in serum, plasma and a platelet sample

  10-12 weeks

• Calculation of the functional VEGF neutralization.

  10-12 weeks

• Neutralization of VEGF in plasma

  10-12 weeks

Other Outcomes (3)

• Measurement of a cellular (T-cell) immune response, as determined by enzyme linked immunospot (ELISPOT)

  26 weeks

• Measurement of immune modulation, through FACS analysis.

  26 weeks

• Measuring angiogenesis suppression within the tumor.

  10-12 weeks

Study Arms (1)

hVEGF26-104/RFASE vaccination

EXPERIMENTAL

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.

Biological: hVEGF26-104/RFASE

Interventions

hVEGF26-104/RFASE BIOLOGICAL

Three intramuscular injections on days 0, 14 and 28, followed by an observational period of 6 weeks. If hererafter VEGF is not (or no longer) neutralized in serum and there is no sign of disease progression, another booster vaccination can be given. This booster can be repeated until disease progression, death or withdrawal from the study.

hVEGF26-104/RFASE vaccination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Immunovo B.V.: collaborator

Study Sites (1)

VU University Medical Center

Amsterdam, North Holland, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Henk Verheul, MD PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: September 11, 2014
• Study Start: April 1, 2014
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: April 19, 2021

Record last verified: 2021-04

Locations

NL (1)