Study of VGX-100 Administered Alone and Co-administered With Bevacizumab in Adult Subjects With Advanced Solid Tumors

Cancer Clinical Trial

Official title:

A Phase I, Open Label, Dose Escalation Study of the VEGF-C Human Monoclonal Antibody VGX-100 Administered by Intravenous Infusion Alone and Co-administered With Bevacizumab in Adult Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01514123
• Other study ID #: VGX-100-1001
• Status: Completed
• Phase: Phase 1
• Start date: December 29, 2011
• Est. completion date: November 16, 2017

Study information

• Verified date: September 2020
• Source: Circadian Technologies Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a non-randomized, multi-dose, first-in-human, multicenter, two arm (Arm A: VGX-100 alone; Arm B: VGX-100 co-administered with bevacizumab), open label, dose escalation study in subjects with advanced or metastatic solid tumors. The study is aimed at evaluating the safety and establishing the recommended dose of the VEGF-C human monoclonal antibody VGX-100 when administered alone or in combination with bevacizumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: November 16, 2017
• Est. primary completion date: February 7, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Provision of written informed consent

• Histologically or cytologically documented advanced or metastatic solid tumor that is refractory to standard treatment, for which no standard therapy is available, or for which the subject refuses standard therapy

• Life expectancy > 3 months in the opinion of the investigator

• ECOG performance status 0 to 1

• Evaluable OR measurable disease by RECIST 1.1 criteria

• Agree to the use of effective contraceptive if either male or female of child bearing potential

Exclusion Criteria:

• Inadequate venous access

• Women who are lactating/breastfeeding

• Women with a positive pregnancy test or who are planning to become pregnant during the duration of the study

• Known to be HIV positive, or have chronic hepatitis B or C

• Major surgical procedure within 6 weeks of Baseline or surgical or other wound that is not fully healed at Baseline

• Untreated or symptomatic brain metastasis, known central nervous system metastasis, or spinal cord compression (except glioblastoma multiforme)

• Mediastinal or cavitated, or lung mass located near, invading or encasing a major blood vessel or airway on imaging

• Squamous cell lung cancer

• History of or known/suspected gastrointestinal perforation

• Hemoptysis of >2.5 mL (half a teaspoon) red blood within 28 days of Screening

• Deep venous thrombosis or history of symptomatic pulmonary thromboembolism within 6 months of Screening

• Gastrointestinal bleeding requiring medical intervention within 28 days of Screening

• Receipt of therapeutic concentrations of warfarin or other anticoagulants within 7 days of Screening

• Receipt of investigational agent(s) for any indication within 28 days of Baseline or 5 half lives, whichever is greater

• Receipt of the following treatments:

• Traditional cytotoxics, tyrosine kinase inhibitors or other small molecule anti-cancer agents within 21 days

• Nitrosoureas, mitomycin C, bevacizumab or trastuzumab within 6 weeks

• Any other therapeutic monoclonal antibodies within 21 days

• Hormonal therapy (other than gonadal suppression) within 14 days

• Radiotherapy:

• to >25% bone marrow

• to brain within 28 days of baseline

• other than above within 14 days of baseline

• Unstable angina, myocardial infarction, transient ischemic events, or stroke within 24 weeks of Screening

• History of CNS hemorrhage, cerebrovascular hemorrhage, myocardial infarction or reversible posterior leukoencephalopathy syndrome associated with prior anti-VEGF/anti-VEGFR therapy

• Uncontrolled hypertension of = CTCAE Grade 2

• Proteinuria at Baseline of =2+ or 1.0g/24 hours

• Prior allergic reaction to a monoclonal antibody

Related Conditions & MeSH terms

• Cancer
• Neoplasms

Intervention

Drug:
• VGX-100
VGX-100 will be administered by IV infusion once every week
• Bevacizumab
Bevacizumab will be administered by IV infusion once every 2 weeks

Locations

Country	Name	City	State
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	UCLA Hematology-Oncology	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Circadian Technologies Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence and severity of adverse events including dose limiting toxicities		Approximately 16 months
Secondary	Tumor response by RECIST criteria	Tumor response assessment will be measured by computated tomography (CT) or Magnetic resonance imaging (MRI) every 8 or 12 weeks throughout the study	Approximately 16 months
Secondary	Pharmacokinetic parameters of VGX-100 alone and co-administered with bevacizumab including Cmax, Cmin, AUC and if feasible half life (t1/2)		28 days after the last subject in each cohort
Secondary	Anti-VGX-100 antibody formation		Approximately 16 months
Secondary	Biomarker levels including VEGF-A, VEGF-C, VEGF-D, soluble VEGFR-2, and soluble VEGFR-3		Approximately 16 months