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

Purpose

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).

Condition	Intervention	Phase
Solid Tumors	Drug: VX15/2503	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Vaccinex Inc.:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Other Outcome Measures:

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 ]


Enrollment:	42
Study Start Date:	January 2011
Study Completion Date:	June 2014
Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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.

Detailed Description:

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.

Eligibility


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

Criteria

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)

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: NCT01313065

Locations


United States, Arizona
Virginia G. Piper Cancer Center at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, Texas
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Vaccinex Inc.

PPD

Investigators


Principal Investigator:	Amita Patnaik, MD	South Texas Accelerated Research Therapeutics, LLC
Principal Investigator:	Ramesh K Ramanathan, MD	TGen Clinical Research Service at Scottsdale Healthcare

More Information

No publications provided by Vaccinex Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Worzfeld T, Offermanns S. Semaphorins and plexins as therapeutic targets. Nat Rev Drug Discov. 2014 Aug;13(8):603-21. doi: 10.1038/nrd4337. Review.


Responsible Party:	Vaccinex Inc.
ClinicalTrials.gov Identifier:	NCT01313065 History of Changes
Other Study ID Numbers:	VX15/2503-01 v.9
Study First Received:	March 4, 2011
Last Updated:	August 11, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Vaccinex Inc.:


VX15/2503 Semaphorin 4D SEMA4D CD100 safety	tolerability pharmacokinetics pharmacodynamics advanced solid tumors

Additional relevant MeSH terms:


Neoplasms

ClinicalTrials.gov processed this record on February 26, 2015