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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Agensys, Inc. )
ClinicalTrials.gov Identifier:
NCT01672775
First received: August 22, 2012
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Carcinoma, Renal Cell
Renal Cell Carcinoma With Clear Cell Histology
Renal Cell Carcinoma With Non-Clear Cell Histology
Renal Cell Carcinoma of Papillary Histology
Drug: AGS-16C3F
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Incidence of Adverse Events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Days 1, 2, 3, 4, 8, 15, 22, 43, 64, 65, 66, 67, 71, 78, and 92 ] [ Designated as safety issue: No ]
    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 (AUCτ), terminal or apparent half-life (t1/2), systemic clearance (CL), and volume of distribution at steady state (Vss)

  • Incidence of antidrug antibody formation to human native antibody (AGS-16C) and antibody drug conjugate (AGS-16C3F) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Tumor response: objective response rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Determined from the subjects' best response and will include complete response (CR) and partial response (PR)

  • Tumor response: disease control rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Determined from the subjects' best response will include complete response (CR) partial response (PR), and stable disease (SD)

  • Tumor response: Changes in bone scans [ Time Frame: Baseline, Week 13 and every 12 weeks thereafter ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: July 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 AGS-16C3F highest dose
Renal Cell Carcinoma subjects with clear and non-clear histology
Drug: AGS-16C3F
intravenous (IV) infusion
Experimental: Cohort 0 AGS-16C3F higher dose
Renal Cell Carcinoma subjects with clear and non-clear histology
Drug: AGS-16C3F
intravenous (IV) infusion
Experimental: Cohort (-1) AGS-16C3F high dose
Renal Cell Carcinoma subjects with clear and non-clear histology
Drug: AGS-16C3F
intravenous (IV) infusion
Experimental: Cohort (-2) AGS-16C3F middle dose
Renal Cell Carcinoma subjects with clear and non-clear histology
Drug: AGS-16C3F
intravenous (IV) infusion
Experimental: Cohort (-3) AGS-16C3F low dose
Renal Cell Carcinoma subjects with clear and non-clear histology
Drug: AGS-16C3F
intravenous (IV) infusion
Experimental: Cohort (-4) AGS-16C3F lowest dose
Renal Cell Carcinoma subjects with clear and non-clear histology
Drug: AGS-16C3F
intravenous (IV) infusion
Experimental: AGS-16C3F in RCC Subjects with Clear Cell Histology
Expansion Cohort
Drug: AGS-16C3F
intravenous (IV) infusion
Experimental: AGS-16C3F in RCC Subjects with Papillary Histology
Expansion Cohort
Drug: AGS-16C3F
intravenous (IV) infusion

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01672775

Locations
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detriot, Michigan, United States, 48201
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Agensys, Inc.
Investigators
Study Director: Medical Director Agensys, Inc.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Agensys, Inc. )
ClinicalTrials.gov Identifier: NCT01672775     History of Changes
Other Study ID Numbers: AGS-16C3F-12-2
Study First Received: August 22, 2012
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Astellas Pharma Inc:
Renal Cell Carcinoma
Pharmacokinetics of AGS-16C3F
AGS-16C3F

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 31, 2014