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

This study has been completed.
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01228760
First received: October 21, 2010
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

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).


Condition Intervention Phase
Prostate Neoplasms
Drug: ASG-5ME
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, Dose Escalation Study of the Safety and Pharmacokinetics of ASG-5ME Monotherapy in Subjects With Castration-Resistant Prostate Cancer (CRPC)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Incidence of tumor response (complete or partial response) [ Time Frame: Baseline and every 12 weeks while on study drug ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Changes in bone scans [ Time Frame: Baseline and every 12 weeks while on study drug ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Changes in cytokeratin-18 levels [ Time Frame: Up to day 79 and 4 weeks after the last dose of study drug ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: October 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 5A 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 9 Drug: ASG-5ME
IV
Experimental: Chemotherapy-naïve subjects Drug: ASG-5ME
IV
Experimental: Chemotherapy exposed subjects Drug: ASG-5ME
IV

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.

  Eligibility

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

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
  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: NCT01228760

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21205
United States, Michigan
The Karmanos Cancer Institute
Detriot, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Wisconsin
University of Wisconsin Madison, Carbone Cancer Center
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Astellas Pharma Inc
Seattle Genetics, Inc.
Investigators
Study Director: Chief Medical Officer Agensys, Inc.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01228760     History of Changes
Other Study ID Numbers: ASG-5ME-10-1
Study First Received: October 21, 2010
Last Updated: June 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Castration-Resistant Prostate Cancer
ASG-5ME
Pharmacokinetics of ASG-5ME

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014