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Trial record 1 of 1 for:    NCT01963052
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ASG-15ME is a Study of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

This study is ongoing, but not recruiting participants.
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 9, 2017
Last verified: June 2017
  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
Intervention Model: Parallel Assignment
Masking: No masking
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

Further study details as provided by Astellas Pharma Inc ( Agensys, Inc. ):

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: up to 36 months ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]

Secondary Outcome Measures:
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: Up to 26 months ]
  • Tumor response [ Time Frame: Up to 26 months ]
    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 ]
    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 ]
    Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)

  • Progression free survival [ Time Frame: Up to 36 months ]
    Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause

  • Overall survival [ Time Frame: Up to 36 months ]
    Time from the date of first infusion until the date of death from any cause

  • Duration of response [ Time Frame: Up to 36 months ]
    Time from the date of the first response CR or PR to the earliest date of disease progression or death from any cause


Enrollment: 93
Actual Study Start Date: November 14, 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: AGS-15E Dose Escalation (Dose Levels 1-6)
Subjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks.
Drug: AGS15E
intravenous (IV) infusion
Experimental: Part B: AGS-15E Cisplatin Therapy -ineligible Expansion
Urothelial subjects who have not received any prior lines of therapy an who are unfit for Cisplatin therapy (Cis-ineligible) will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will initially be dosed one dose level below the preliminary recommended phase 2 dose (RP2D).
Drug: AGS15E
intravenous (IV) infusion
Experimental: Part C: AGS15E Immune Checkpoint Inhibitor Treated Expansion
Subjects previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will be dosed at the RP2D.
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, investigator decision, or consent withdrawal.

In subjects who discontinue therapy without documented disease progression and who still consent to study procedures, every effort should be made to continue monitoring their disease status by radiographic imaging until progression is documented, or new anticancer therapy, or death. All subjects will continue to be followed for survival until withdrawal of consent or study closure.

If assessed as complete response (CR) or partial response (PR) per local review a confirmatory scan will be performed no less than 4 weeks from previous scan and preferably at week 5. Tumor imaging should also be performed whenever disease progression is suspected.

Images will be sent to a central third party imaging vendor for an independent assessment per RECIST version 1.1. Although the imaging studies will be reviewed by a central third party imaging vendor in a retrospective fashion, all clinical decisions will be based on the interpretation of the investigator at the site treating the subject.

Post-Treatment Follow-up Progression Free Survival: Subjects who discontinued the study for reasons other than objective disease progression will continue disease assessments until radiologically confirmed progression, initiates a new anticancer therapy, death, loss to follow-up or withdraw consent for further follow-up, whichever of these events occurs first. The purpose of the post-treatment follow-up is to ascertain the duration of progression-free survival for all subjects enrolled in the study.

Overall survival: All subjects will be followed by telephone contact every 2 months until death, loss to follow-up, or withdrawal of consent, whichever of these events occurs first. A standard of care clinic visit can be used in lieu of a telephone call, if the subject is already coming to clinic.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
  • Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy.
  • Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed).
  • Part C (CPI-Treated Expansion): Subject must have received prior treatment with a CPI in the metastatic setting
  • Subjects must have measureable disease according to RECIST (version 1.1).
  • Part A and C: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Part B: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Life expectancy of ≥ 3 months
  • Adequate hematologic function
  • Parts A and C: Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min
  • Part B: Renal function, as follows: creatinine clearance estimate ≥ 15 mL/min and <60 mL/min by cockroft gault equation adjusted for body weight
  • Adequate liver function

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 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 (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)
  • Subjects with Immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible
  • 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
  • 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
  • Known HIV or AIDS
  • 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
  • Known sensitivity to any of the ingredients of the investigational product AGS15E
  • Major surgery within 28 days prior to first dose of study drug
  • 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
  • History of uncontrolled diabetes mellitus or diabetic neuropathy
  • Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
  • Has ocular conditions such as:

    • Active infection or corneal ulcer (e.g., keratitis)
    • Monocularity
    • History of corneal transplantation
    • Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
    • Uncontrolled glaucoma (topical medications allowed)
    • Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder
  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

Locations
United States, Alabama
Site US00006
Birmingham, Alabama, United States, 35294
United States, Connecticut
Site US00002
New Haven, Connecticut, United States, 06510
United States, Michigan
Site US00001
Detroit, Michigan, United States, 48201
United States, Missouri
Site US00003
Saint Louis, Missouri, United States, 63110
United States, New York
Site US00009
Buffalo, New York, United States, 14263
United States, Tennessee
Site US00010
Nashville, Tennessee, United States, 37212
United States, Washington
Site US00008
Seattle, Washington, United States, 98109
Canada, British Columbia
Site CA00004
Vancouver, British Columbia, Canada, V5Z 1H5
Canada, Ontario
Site CA00007
Hamilton, Ontario, Canada, L8V 5C2
Site CA00005
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Agensys, Inc.
Seattle Genetics, Inc.
Investigators
Study Director: Medical Director Agensys, Inc.
  More Information

Responsible Party: 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 9, 2017

Keywords provided by Astellas Pharma Inc ( Agensys, Inc. ):
Metastatic Urothelial Cancer
AGS15E
AGS15E-13-1
ASG-15ME
Pharmacokinetics of AGS15E

ClinicalTrials.gov processed this record on June 27, 2017