Trial record 1 of 1 for:    NCT01963052
Previous Study | Return to List | Next Study

ASG-15ME is a Study of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Astellas Pharma Inc
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Agensys, Inc. )
ClinicalTrials.gov Identifier:
NCT01963052
First received: October 7, 2013
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

The objectives of this study are to assess the safety, pharmacokinetics, immunogenicity and anti-tumor activity of AGS15E in subjects with metastatic urothelial cancer who failed at least one prior chemotherapy regimen for metastatic disease.


Condition Intervention Phase
Metastatic Urothelial Cancer
Drug: AGS15E
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 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: up to 26 months ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss) [ Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: Up to 26 months ] [ Designated as safety issue: No ]
  • Tumor response [ Time Frame: Up to 26 months ] [ Designated as safety issue: No ]
    Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per RECIST criteria (version 1.1) that should be confirmed ≥ 28 days later

  • Objective response rate [ Time Frame: Up to 26 months ] [ Designated as safety issue: No ]
    Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR should be confirmed ≥ 28 days later.

  • Disease control rate [ Time Frame: Up to 26 months ] [ Designated as safety issue: No ]
    Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)


Estimated Enrollment: 45
Study Start Date: August 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AGS15E Dose Level 1 Drug: AGS15E
intravenous (IV) infusion
Experimental: AGS15E Dose Level 2 Drug: AGS15E
intravenous (IV) infusion
Experimental: AGS15E Dose Level 3 Drug: AGS15E
intravenous (IV) infusion
Experimental: AGS15E Dose Level 4 Drug: AGS15E
intravenous (IV) infusion
Experimental: AGS15E Dose Level 5 Drug: AGS15E
intravenous (IV) infusion
Experimental: AGS15E Dose Level 6 Drug: AGS15E
intravenous (IV) infusion

Detailed Description:

All subjects will receive a single intravenous infusion of AGS15E once weekly for 3 weeks of every 4 weeks. A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of AGS15E or consent withdrawal.

The study design will follow a modified Continual Reassessment Method (CRM). A disease assessment will be conducted every 8 weeks (Q8W) +/- 7 days until disease progression.

A data review team (DRT) will review cumulative unaudited data on an interim basis to explore additional doses and/or schedules, or the expansion of existing cohorts. Doses intermediate to those predefined in the protocol may be explored with DRT endorsement.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra).
  • Must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy
  • Subjects must have measureable disease according to RECIST (version 1.1)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of ≥ 3 months
  • Adequate hematologic function
  • Adequate renal function
  • Adequate liver function
  • Lipase within the normal range
  • Amylase ≤ 1.5 x ULN

Exclusion Criteria:

  • Preexisting sensory neuropathy Grade ≥ 2 or motor neuropathy Grade ≥ 2
  • Uncontrolled central nervous system metastases
  • Use of any investigational drug within 14 days or 5 half-lives prior to the first dose of study drug Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer within 14 days prior to the first dose of study drug
  • Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug
  • History of thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug
  • Positive Hepatitis B surface antigen test
  • Positive Hepatitis C antibody test
  • Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
  • History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit:

    • Non-melanoma skin cancer;
    • adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable;
    • cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and
    • definitively treated, stage I/II ER+ breast cancer
  • Active infection requiring treatment ≤7 days before first dose of study drug
  • Condition or situation which, in the investigator's opinion, may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
  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: NCT01963052

Contacts
Contact: Agensys Clinical Research and Development 424-280-5000 Clinical@Agensys.com

Locations
United States, Alabama
University of Alabama at Birmingham (UAB) Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35294
United States, Connecticut
Smilow Cancer Center at Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
United States, Michigan
Karmanos Recruiting
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University Medical School Recruiting
St. Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Tisch Cancer Institute of Mt. Sinai School of Medicine Withdrawn
New York, New York, United States, 10029
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Canada, British Columbia
British Columbia Cancer Agency Recruiting
Vancouver, British Columbia, Canada, V5Z 1H5
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Sunnybrook Cancer Institute Recruiting
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Agensys, Inc.
Seattle Genetics, Inc.
Investigators
Study Director: Medical Director Agensys, Inc.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Agensys, Inc. )
ClinicalTrials.gov Identifier: NCT01963052     History of Changes
Other Study ID Numbers: AGS15E-13-1
Study First Received: October 7, 2013
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Astellas Pharma Inc:
Metastatic Urothelial Cancer
Pharmacokinetics of AGS15E
AGS15E
ASG-15ME
AGS15E-13-1

ClinicalTrials.gov processed this record on October 21, 2014