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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Circadian Technologies Ltd.
ClinicalTrials.gov Identifier:
NCT01514123
First received: January 12, 2012
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Neoplasms
Cancer
Drug: VGX-100
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Circadian Technologies Ltd.:

Primary Outcome Measures:
  • The incidence and severity of adverse events including dose limiting toxicities [ Time Frame: Approximately 16 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response by RECIST criteria [ Time Frame: Approximately 16 months ] [ Designated as safety issue: No ]
    Tumor response assessment will be measured by computated tomography (CT) or Magnetic resonance imaging (MRI) every 8 or 12 weeks throughout the study

  • Pharmacokinetic parameters of VGX-100 alone and co-administered with bevacizumab including Cmax, Cmin, AUC and if feasible half life (t1/2) [ Time Frame: 28 days after the last subject in each cohort ] [ Designated as safety issue: No ]
  • Anti-VGX-100 antibody formation [ Time Frame: Approximately 16 months ] [ Designated as safety issue: Yes ]
  • Biomarker levels including VEGF-A, VEGF-C, VEGF-D, soluble VEGFR-2, and soluble VEGFR-3 [ Time Frame: Approximately 16 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A - VGX-100 alone
Dose escalation of VGX-100 monotherapy
Drug: VGX-100
VGX-100 will be administered by IV infusion once every week
Experimental: Arm B - VGX-100 plus bevacizumab
Dose escalation of VGX-100 in combination with escalating doses of bevacizumab
Drug: VGX-100
VGX-100 will be administered by IV infusion once every week
Drug: Bevacizumab
Bevacizumab will be administered by IV infusion once every 2 weeks
Other Name: Avastin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01514123

Locations
United States, California
UCLA Hematology-Oncology
Santa Monica, California, United States, 90404
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Circadian Technologies Ltd.
Investigators
Study Director: Clinical Research Circadian Technologies
  More Information

No publications provided

Responsible Party: Circadian Technologies Ltd.
ClinicalTrials.gov Identifier: NCT01514123     History of Changes
Other Study ID Numbers: VGX-100-1001
Study First Received: January 12, 2012
Last Updated: February 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Circadian Technologies Ltd.:
VGX-100
Bevacizumab
VEGF-C
First-In-Human
Dose Escalation
Advanced Solid Tumors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Pharmacologic Actions
Antibodies, Monoclonal
Phase 1
Oncology
Advanced malignancy

Additional relevant MeSH terms:
Bevacizumab
Angiogenesis Modulating Agents
Angiogenesis Inhibitors
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014