Evaluation of Safety, Tolerability, PK & PD of Intravenous VX15/2503 in Patients With Advanced Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
Vaccinex Inc.
ClinicalTrials.gov Identifier:
NCT01313065
First received: March 4, 2011
Last updated: December 16, 2013
Last verified: December 2013

March 4, 2011
December 16, 2013
January 2011
June 2014   (final data collection date for primary outcome measure)
  • Safety/tolerability as measured by number of patients with adverse events [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]
    Subject incidence of treatment-emergent adverse events
  • Maximum tolerated dose as measured by frequency of dose limiting toxicities [ Time Frame: Four (4) weeks after first dose ] [ Designated as safety issue: Yes ]
  • Safety/tolerability as measured by number of patients with adverse events [ Time Frame: Up to one (1) year ] [ Designated as safety issue: Yes ]
    Subject incidence of treatment-emergent adverse events
  • Maximum tolerated dose as measured by frequency of dose limiting toxicities [ Time Frame: Six (6) weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01313065 on ClinicalTrials.gov Archive Site
  • Peak plasma concentration (Cmax) of VX15/2503 [ Time Frame: Four (4) hours after start of infusion ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) of VX15/2503 [ Time Frame: Up to seven (7) days after first dose ] [ Designated as safety issue: No ]
  • Half-life of VX15/2503 [ Time Frame: Up to 14 days after first dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics as measured by Cmax, CL, Vd, Vss and AUCs [ Time Frame: 0,1,4,8,24,48,96,148,240 and 336 hours after start of infusion ] [ Designated as safety issue: No ]
  • Pharmacodynamics as measured by SEMA4D T cell saturation [ Time Frame: 0,1,4,8,24,48,96,148, 240 and 336 hours after start of infusion ] [ Designated as safety issue: No ]
  • Immunogenicity as measured by number of patients who develop anti-drug antibody [ Time Frame: Up to one (1) year ] [ Designated as safety issue: No ]
  • SEMA4D T cell percent saturation of VX15/2503 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Number of patients who develop anti-drug antibody [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Overall response rate (ORR) using RECIST 1.1 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) using RECIST 1.1 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
Not Provided
 
Evaluation of Safety, Tolerability, PK & PD of Intravenous VX15/2503 in Patients With Advanced Solid Tumors
A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous Infusion of VX15/2503 in Adult Patients With Advanced Solid Tumors

The purpose of this study is to evaluate the safety and tolerability of IV administration of VX15/2503 in patients with advanced solid tumors. The escalation part of the study will determine the maximum tolerated dose (MTD).

VX15/2503-01 is a dose-escalation, open label study to evaluate the safety and tolerability of IV administered VX15/2503 in patients with advanced solid tumors. This will be accomplished by using a dose escalation procedure starting at low doses of VX15/2503 and will continue based on predefined parameters until the maximum tolerated dose is identified.

The study drug, VX15/2503, is a monoclonal antibody that binds to the semaphorin 4D (SEMA4D; CD100) antigen. Semaphorins have been shown to play an important role in certain physiological processes such as vascular growth, tumor progression and immune cell regulation. Experimental evidence suggests that SEMA4D has two mechanisms of action that result in angiogenesis and tumor proliferation and invasion. Antibody neutralization of SEMA4D thus may represent a new therapeutic strategy for cancer treatment.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Solid Tumors
Drug: VX15/2503
Dose escalation will begin at low doses and will gradually increase in each future cohort. The current trial design provides for 7 study cohorts with a 20 mg/kg expansion phase.
Experimental: VX15/2503
VX15/2503 monoclonal antibody at a concentration of 0.3 mg/kg - 20 mg/kg to be administered intravenously on a weekly dosing cycle.
Intervention: Drug: VX15/2503
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
64
October 2014
June 2014   (final data collection date for primary outcome measure)

Main Inclusion Criteria:

  • Patients 18 yrs or older with confirmed histological or cytological advanced solid tumors, relapsed or refractory to standard treatment for which no curative therapy is available; patients must demonstrate progressive disease prior to entry
  • Has measurable disease as defined by RECIST1.1
  • Life expectancy of at least 3 months (per investigator assessment)
  • ECOG performance status of 0-2
  • Adequate bone marrow, renal and liver function
  • Recovered from any significant prior toxicity of previous anti-neoplastic therapy
  • For patients of reproductive potential, is willing to use a medically acceptable form of contraception throughout the study period and for at least 4 weeks after the last dose of VX15/2503
  • Expansion cohort - patients in this cohort must have one of the following characteristics:
  • A diagnosis of a pancreatic neuroendocrine tumor OR
  • A diagnosis of a soft tissue sarcoma OR
  • A diagnosis of a bone metastasis OR
  • A diagnosis of advanced solid tumor AND a T cell count of at least 1500 cells/uL OR a B cell count of at least 250 cells/uL at screening

Main Exclusion Criteria:

  • Treatment with anti-neoplastic agents (chemotherapy, immunotherapy, radiotherapy or endocrine therapy) within 3 weeks prior to start of study treatment
  • Treatment with an investigational agent within 4 weeks prior to start of study treatment
  • Is on concurrent anti-neoplastic therapy with the exception of continuing luteinizing hormone-releasing hormone agonist/antagonist therapy for patients with castrate-resistant prostate cancer
  • Treatment with oral or parenteral corticosteroids in excess of 10mg/day of prednisolone or equivalent for more than 5 days within 4 weeks prior to start of study treatment or a requirement for systemic immunosuppressive therapy for any reason
  • Untreated brain Mets or CNS tumor involvement
  • Any other intercurrent illness or condition which could impact patient compliance or ability to complete the study
  • Sensitivity to VX15/2503 or the ingredients or excipients of VX15/2503
  • Pregnant or breast-feeding women (women of child-bearing potential must have negative serum pregnancy test within 3 days prior to receiving the first dose of VX15/2503)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01313065
VX15/2503-01 v.9
No
Vaccinex Inc.
Vaccinex Inc.
PPD
Principal Investigator: Amita Patnaik, MD South Texas Accelerated Research Therapeutics, LLC
Principal Investigator: Ramesh K Ramanathan, MD TGen Clinical Research Service at Scottsdale Healthcare
Vaccinex Inc.
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP