Clinical trial NCT01672775: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Renal Cell
Renal Cell Carcinoma of Papillary Histology
Renal Cell Carcinoma With Clear Cell Histology
Renal Cell Carcinoma With Non-Clear Cell Histology
Keywords: Renal Cell Carcinoma
AGS-16C3F
Pharmacokinetics of AGS-16C3F
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-08-27
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: 24 months
Secondary outcomes:
measure: Pharmacokinetic profile for total antibody (TAb), antibody drug conjugate (ADC), and monomethyl auristatin F (MMAF): Ceoi or Cmax, Ctrough, Tmax, AUCτ, t1/2, CL, and Vss
timeFrame: Days 1, 2, 3, 4, 8, 15, 22, 43, 64, 65, 66, 67, 71, 78, and 92
measure: Incidence of antidrug antibody formation to human native antibody (AGS-16C) and antibody drug conjugate (AGS-16C3F)
timeFrame: 24 months
measure: Tumor response: objective response rate
timeFrame: 24 months
measure: Tumor response: disease control rate
timeFrame: 24 months
measure: Tumor response: Changes in bone scans
timeFrame: Baseline, Week 13 and every 12 weeks thereafter
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: Site US00005 University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Site US00003 Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Site US00004 Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Site US00002 Memorial Sloan-Kettering Cancer Center
state: New York
city: Seattle
country: United States
facility: Site US00001 Seattle Cancer Care Alliance
state: Washington
city: Edmonton
country: Canada
facility: Site CA00006 Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: Site CA00008 British Columbia Cancer Agency
state: British Columbia
city: London
country: Canada
facility: Site CA00009 London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Site CA00007 Jewish General Hospital
state: Quebec
Study officials:
affiliation: Agensys, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: