Clinical trial NCT01514123: Study of VGX-100 Administered Alone and Co-administered With Bevacizumab in Adult Subjects With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Cancer
Keywords: 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
Lead sponsor: Circadian Technologies Ltd.
Sponsor class: INDUSTRY
First posted: 2012-01-20
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: The incidence and severity of adverse events including dose limiting toxicities
timeFrame: Approximately 16 months
Secondary outcomes:
measure: Tumor response by RECIST criteria
timeFrame: Approximately 16 months
measure: Pharmacokinetic parameters of VGX-100 alone and co-administered with bevacizumab including Cmax, Cmin, AUC and if feasible half life (t1/2)
timeFrame: 28 days after the last subject in each cohort
measure: Anti-VGX-100 antibody formation
timeFrame: Approximately 16 months
measure: Biomarker levels including VEGF-A, VEGF-C, VEGF-D, soluble VEGFR-2, and soluble VEGFR-3
timeFrame: Approximately 16 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Hematology-Oncology
state: California
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Circadian Technologies
name: Clinical Research
role: STUDY_DIRECTOR
References: