A Study to Determine the Maximum Tolerated Dose of ASG-5ME in Subjects With Castration-Resistant Prostate Cancer

June 6, 2013 updated by: Astellas Pharma Inc

A Phase 1, Open-label, Multi-center, Dose Escalation Study of the Safety and Pharmacokinetics of ASG-5ME Monotherapy in Subjects With Castration-Resistant Prostate Cancer (CRPC)

The purpose of this dose escalation study is to determine the Maximum Tolerated Dose (MTD) and the recommended Phase 2 dose of ASG-5ME in subjects with castration-resistant prostate cancer (CRPC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study has two components. The first aims to establish a safe dose of ASG-5ME. Once identified, the safety and preliminary estimate of antitumor activity of ASG-5ME will be tested in additional subjects with castration-resistant prostate cancer (CRPC) who are either chemotherapy naïve or chemotherapy exposed in expanded cohorts.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • The Sidney Kimmel Comprehensive Cancer Center
    • Michigan
      • Detriot, Michigan, United States, 48201
        • The Karmanos Cancer Institute
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan Kettering Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin Madison, Carbone Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Subject has histologically-confirmed castration-resistant prostate cancer and meets at least 1 of the following criteria:

    • subject's disease has progressed on or after available standard therapy -OR-
    • there is no effective standard therapy available for treating the subject's disease -OR-
    • subject or his disease is not suitable for standard therapy -OR-
    • subject chooses to defer or decline standard therapy (subject is adequately informed of the availability of clinically meaningful therapy and chooses instead to partake in this research using a product with no documented clinical activity)
  • Testosterone ≤ 50 ng/dL
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of > 6 months as evaluated and documented by the investigator

  • Hematologic function, as follows (no red blood cell (RBC) or platelet transfusions are allowed within 4 weeks of the first dose of ASG-5ME):

    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Platelet count ≥ 100 x 109/L
    • Hemoglobin ≥ 9 g/dL
  • Renal function, as follows: creatinine ≤ 1.5 x upper limit of normal (ULN), or creatinine clearance of > 60 mL/min if serum creatinine is > 2.0 mg/dL
  • Total bilirubin < 1. 5 x ULN
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)≤ 1.5 x ULN
  • International Normalized Ratio (INR) < 1.3 (or < 3.0 if on therapeutic anticoagulation)
  • Serum calcium ≤ ULN
  • Subjects must be taking and agree to remain on a stable dose of luteinizing hormone-releasing hormone (LHRH) agonist therapy or gonadotropin-releasing hormone (GnRH) antagonist for the duration of the trial if not surgically castrated
  • Additional Inclusion criteria for Chemotherapy Naïve Cohort: No prior systemic cytotoxic chemotherapies

  • Additional Inclusion criteria for Chemotherapy Exposed Cohort:

    • Documented disease progression during or after docetaxel treatment or intolerability to docetaxel treatment
    • No additional prior chemotherapy for CRPC is allowed

Exclusion Criteria:

  • History of central nervous system metastasis, including incompletely treated epidural disease

  • History of other primary malignancy (including premalignant myeloid malignancy e.g. myelodysplastic syndrome), unless:

    • Curatively resected non-melanomatous skin cancer
    • Other malignancy curatively treated with no known active disease present and no treatment administered for the last 3 years
  • 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 outsubject medication
  • The following treatments are not allowed within 4 weeks of enrollment: cytotoxic chemotherapy, radiation therapy or the dietary supplement PC-SPES
  • Use of prednisone (or equivalent corticosteroids) > 20 mg/day are not allowed. Doses < 20 mg/day are allowed only if they have been at the same dose for > 4 weeks
  • Use of anti-androgen therapy (ie, flutamide, bicalutamide and nilutamide) within 6 weeks of study enrollment; non-responders to second-line anti-androgen therapy do not require the 6 week withdrawal period
  • Monoclonal antibody therapy within 3 months of enrollment with the exception of denosumab (prior or concurrent use of denosumab is allowed)
  • Peripheral neuropathy of ≥ grade 2 as defined by the CTCAE criteria version 4.0
  • Major surgery (that requires general anesthesia) within 4 weeks of study enrollment
  • Active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) within 72 hours of screening
  • Use of any investigational drug (including marketed drugs not approved for this indication) within 30 days prior to enrollment
  • History of thromboembolic events and bleeding disorders ≤ 3 months (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE))
  • Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose level 1
Drug: ASG-5ME
IV
Experimental: Dose level 2
Drug: ASG-5ME
IV
Experimental: Dose level 3
Drug: ASG-5ME
IV
Experimental: Dose level 4
Drug: ASG-5ME
IV
Experimental: Dose level 5
Drug: ASG-5ME
IV
Experimental: Dose level 6
Drug: ASG-5ME
IV
Experimental: Dose level 7
Drug: ASG-5ME
IV
Experimental: Dose level 8
Drug: ASG-5ME
IV
Experimental: Dose level 5A
Drug: ASG-5ME
IV
Experimental: Dose level 9
Drug: ASG-5ME
IV
Experimental: Chemotherapy-naïve subjects
Drug: ASG-5ME
IV
Experimental: Chemotherapy exposed subjects
Drug: ASG-5ME
IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety assessed by recording of adverse events, laboratory assessments and vital signs
Time Frame: For 12 weeks during treatment period and up to 4 weeks follow up
For 12 weeks during treatment period and up to 4 weeks follow up
Pharmacokinetics assessment of ASG-5ME blood levels through analysis of blood samples
Time Frame: Up to day 15 for cycle 1 and cycle 4 and pre-dose for cycles 2 and 3; every 3 weeks during the second 12 weeks of treatment; and if subject continues on study drug, every 12 weeks thereafter
Up to day 15 for cycle 1 and cycle 4 and pre-dose for cycles 2 and 3; every 3 weeks during the second 12 weeks of treatment; and if subject continues on study drug, every 12 weeks thereafter

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of anti-ASG-5ME antibody formation
Time Frame: Baseline; up to day 64 during the first 12 weeks; and if subject continues on study drug, every 3 weeks during the second 12 weeks of treatment and every 12 weeks thereafter
Baseline; up to day 64 during the first 12 weeks; and if subject continues on study drug, every 3 weeks during the second 12 weeks of treatment and every 12 weeks thereafter
Incidence of tumor response (complete or partial response)
Time Frame: Baseline and every 12 weeks while on study drug
Baseline and every 12 weeks while on study drug
Changes in prostate-specific antigen (PSA) levels
Time Frame: Baseline; up to day 64 during the first 12 weeks; and if the subject continues on study drug, every 3 weeks thereafter
Baseline; up to day 64 during the first 12 weeks; and if the subject continues on study drug, every 3 weeks thereafter
Changes in bone scans
Time Frame: Baseline and every 12 weeks while on study drug
Baseline and every 12 weeks while on study drug
Changes in circulating tumor cells
Time Frame: Baseline; up to day 64 during the first 12 weeks; and if the subject continues on study drug, every 3 weeks during the second 12 weeks of treatment and every 12 weeks thereafter
Baseline; up to day 64 during the first 12 weeks; and if the subject continues on study drug, every 3 weeks during the second 12 weeks of treatment and every 12 weeks thereafter
Changes in cytokeratin-18 levels
Time Frame: Up to day 79 and 4 weeks after the last dose of study drug
Up to day 79 and 4 weeks after the last dose of study drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Astellas Pharma Inc

Collaborators

Seagen Inc.

Investigators

  • Study Director: Chief Medical Officer, Agensys, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

October 21, 2010

First Submitted That Met QC Criteria

October 25, 2010

First Posted (Estimate)

October 26, 2010

Study Record Updates

Last Update Posted (Estimate)

June 7, 2013

Last Update Submitted That Met QC Criteria

June 6, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASG-5ME-10-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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