A Study to Assess the Safety, Pharmacokinetics and Effectiveness of AGS-16C3F Monotherapy in Subjects With Renal Cell Carcinoma (RCC) of Clear Cell or Papillary Histology

Carcinoma, Renal Cell Clinical Trial

Official title:

A Phase 1, Open Label, Multi-center Study to Assess the Safety, Pharmacokinetics and Effectiveness of AGS-16C3F Monotherapy in Subjects With Renal Cell Carcinoma (RCC) of Clear Cell or Papillary Histology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01672775
• Other study ID #: AGS-16C3F-12-2
• Status: Completed
• Phase: Phase 1
• Start date: July 18, 2012
• Est. completion date: February 21, 2017

Study information

• Verified date: December 2020
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and pharmacokinetics and assess the immunogenicity and effectiveness of AGS-16C3F in subjects with renal cell cancer (RCC).

Description:

The study has two components. The first aims to establish a safe dose for AGS-16C3F. Once identified, the safety and effectiveness will be tested in additional subjects with either clear cell or papillary histology in expanded cohorts.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: February 21, 2017
• Est. primary completion date: February 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Dose determination cohorts: Histologically confirmed diagnosis of metastatic RCC of either clear cell or non-clear histology.
• Tumors with clear cell histology: subject must have progressed after at least one anti-vascular endothelial growth factor receptor (anti-VEGFR) therapy
• Tumors with non-clear cell histology must be ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3) positive at pre-screening. This sub-group does not have any prior therapy requirement.
• Dose expansion cohorts: Histologically confirmed diagnosis of metastatic RCC of either clear cell or papillary histology
• Tumors with clear cell histology: subject must have progressed after at least one anti-VEGFR therapy
• Tumors with papillary histology: includes unclassified histology with papillary features and must be ENPP3 positive at pre-screening. This sub-group does not have any prior therapy requirement.
• Measurable disease according to Response Criteria for Solid Tumors (RECIST Version 1.1)
• Eastern Cooperative Group (ECOG) performance status of 0-1
• Hematologic function, as follows:
• Absolute neutrophil count (ANC) = 1.5 x 109/L
• Platelet count = 100 x 109/L
• Hemoglobin = 9 g/dL (transfusions are allowed)
• Renal function, as follows:
• creatinine = 1.5 x upper limit of normal (ULN), or calculated glomerular filtration rate (GFR) > 50 mL/min if creatinine > 1.5x ULN
• Hepatic function, as follows:
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2.5 x ULN or = 5x ULN if known liver metastases
• Total bilirubin =1.5 x ULN
• International normalized ratio (INR) < 1.3 (or = 3.0 if on therapeutic anticoagulation)
• Women and men of childbearing potential must be advised and agree to practice effective methods of contraception during the course of the study and for 4 weeks after the last AGS-16C3F infusion administration

Exclusion Criteria:

• Current uncontrolled central nervous system (CNS) metastasis or malignant brain tumors
• Use of any investigational drug (including marketed drugs not approved for this indication) within 4 weeks prior to screening. No time limit applies to the use of marketed drugs approved for this indication provided that the subject has progressed on the treatment and all toxicities attributable to the drug have resolved or returned to baseline
• Known sensitivity to any of the ingredients of the investigational product AGS-16C3F
• History of thromboembolic events and bleeding disorders =3 months (e.g., (deep vein thrombosis) DVT or pulmonary embolism (PE))
• Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication.
• Major surgery within 4 weeks of study enrollment
• Women who are pregnant (confirmed by positive pregnancy test) or lactating
• Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen.
• Active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) within 72 hours of screening.
• History of eye surgery within 6 months, presence of cataracts or other ocular disorders significantly affecting vision

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma of Papillary Histology
• Renal Cell Carcinoma With Clear Cell Histology
• Renal Cell Carcinoma With Non-Clear Cell Histology

Intervention

Drug:
• AGS-16C3F
intravenous (IV) infusion

Locations

Country	Name	City	State
Canada	Site CA00006 Cross Cancer Institute	Edmonton	Alberta
Canada	Site CA00009 London Health Sciences Centre	London	Ontario
Canada	Site CA00007 Jewish General Hospital	Montreal	Quebec
Canada	Site CA00008 British Columbia Cancer Agency	Vancouver	British Columbia
United States	Site US00005 University of Michigan Medical Center	Ann Arbor	Michigan
United States	Site US00004 Roswell Park Cancer Institute	Buffalo	New York
United States	Site US00003 Karmanos Cancer Institute	Detroit	Michigan
United States	Site US00002 Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Site US00001 Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Agensys, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events		24 months
Secondary	Pharmacokinetic profile for total antibody (TAb), antibody drug conjugate (ADC), and monomethyl auristatin F (MMAF): Ceoi or Cmax, Ctrough, Tmax, AUCt, t1/2, CL, and Vss	Concentration at end of infusion (Ceoi) or maximum observed concentrations (Cmax), Trough concentration (Ctrough), time to maximum concentration (Tmax), partial area under the serum concentration-time curve (AUCt), terminal or apparent half-life (t1/2), systemic clearance (CL), and volume of distribution at steady state (Vss)	Days 1, 2, 3, 4, 8, 15, 22, 43, 64, 65, 66, 67, 71, 78, and 92
Secondary	Incidence of antidrug antibody formation to human native antibody (AGS-16C) and antibody drug conjugate (AGS-16C3F)		24 months
Secondary	Tumor response: objective response rate	Determined from the subjects' best response and will include complete response (CR) and partial response (PR)	24 months
Secondary	Tumor response: disease control rate	Determined from the subjects' best response will include complete response (CR) partial response (PR), and stable disease (SD)	24 months
Secondary	Tumor response: Changes in bone scans		Baseline, Week 13 and every 12 weeks thereafter

External Links

•   Link to results on the Astellas Clinical Study Results website.